Abstract
The role of PLAC8 in tumorigenesis has been gradually elucidated with the development of research. Although there are common molecular mechanisms that enforce cell growth, the impact of PLAC8 is varied and can, in some instances, have opposite effects on tumorigenesis. To systematically understand the role of PLAC8 in tumors, the molecular functions of PLAC8 in cancer will be discussed by focusing on how PLAC8 impacts tumorigenesis when it arises within tumor cells and how these roles can change in different stages of cancer progression with the ultimate goal of suppressing PLAC8-relevant cancer behavior and related pathologies. In addition, we highlight the diversity of PLAC8 in different tumors and its functional output beyond cancer cell growth. The comprehension of PLAC8’s molecular function might provide new target and lead to the development of novel anticancer therapies.
Similar content being viewed by others
Introduction
Placenta specific 8 (PLAC8), also known as Onzin, C15, DGIC and PNAS-144, was first identified in genome-wide expression profiling of mid-gestation placentas and embryos using a 15,000 mouse-developmental cDNA microarray [1, 2]. PLAC8 expression is dynamic during pregnancy and placental development and accumulates in an implantation-dependent manner [1, 3]. PLAC8 has also been found to be involved in embryo development [4,5,6,7,8]. And PLAC8 is found to be highly expressed in the endometrium of pregnant cows compared to nonpregnant cows, and it is upregulated in blastocysts, resulting in calf delivery [9,10,11,12]. Subsequent research on PLAC8 was not limited to animals but also involved humans and many plants [13,14,15,16]. During the differentiation process of cytotrophoblast cells into interstitial extravillous trophoblast cells, PLAC8 is greatly induced [17]. To date, PLAC8 has been determined to be involved in organ development and tumorigenesis [18,19,20,21]. In addition, PLAC8 is a molecular marker to predict prognosis and distinguish between different cell subpopulations [17, 22]. PLAC8 also plays different roles in a cell- or tissue-type specific manner. Throughout this review, we discuss the structure of PLAC8 and how PLAC8 evokes widely different responses in tumorigenesis.
PLAC8 protein
The PLAC8 gene is located in human chromosome 4 and Mus musculus chromosome 5, which is one of the placenta-regulatory genes and belongs to the cornifelin family.
The PLAC8 protein contains five exons, coding for a mRNA species of 829 bp and an open reading frame of 115 amino acids [1], which shows a high degree of conservation (83%) between humans and mice [1, 23]. In addition, FW2.2-like (FWL) genes which are identified in plant species and PLAC8 genes, which both contain highly conserved cysteine-rich motifs, share a common ancestor before the divergence between plants and animals [24]. The first 11 amino acids of this cysteine-rich domain are reported to be required for binding of PLAC8 with Akt1 and MDM-2 protein, and then regulate the activity of Akt1 and MDM-2 [25]. This same region is also found to be required for PLAC8 transiently binds to the C/EBPβ promoter and induce its transcription [26]. In addition, this cysteine-rich domain is called the PLAC8 motif which does not conform to consensus zinc- or RING-finger domains [27, 28]. The PLAC8 motif-containing proteins form a large family and members which can be found in fungi, algae, higher plants and animals [29, 30]. In plants, AtPCR1 and AtPCR2 which contain PLAC8 motif play an important role in transport of heavy metals such as cadmium or zinc [29]. However, our knowledge about the function of PLAC8 motif-containing proteins is very limited. To some extent, although PLAC8 protein has only 115 amino acids (Fig. 1), investigation of its intact domain will help to provide a full understanding of its function and PLAC8 motif-containing proteins.
PLAC8 structure. The cysteine-rich domain of the human PLAC8 protein is located between amino acids 28 and 61
PLAC8 protein does not have an N-terminal signal peptide, indicating that this protein is not a secretory protein and functions within the cytoplasm or the nucleus [31]. And the precise cellular location of PLAC8 varies greatly depending on its specific context. For instance, the intracellular distribution of the PLAC8 protein is dynamic and regulated in an implantation-dependent manner [32]. PLAC8 is specifically expressed in the interstitial extravillous trophoblast cells on the fetomaternal interface, while its expression is hardly detectable in the endovasculare trophoblast cells [17]. PLAC8 is found exclusively at the apical domain of fully differentiated normal colonic epithelium in both colonocytes and goblet cells [33], and it localizes at the trophoblast cell periphery [17]. In addition, PLAC8 has been found in nasopharyngeal carcinoma and breast cancer cell cytoplasm and membrane [34, 35]. After breast cancer cells acquired drug resistance, PLAC8 accumulated both in nucleus and cytoplasm [36]. In pancreatic cancer cells, PLAC8 is located in the inner plasma membrane [37]. However, in pancreatic ductal adenocarcinoma, PLAC8 is mainly located in lysosomes [38]. The lysosomes contain transporters and participates in the export of molecules [39]. The location of PLAC8 in lysosomes might cause the different location of PLAC8 because of lysosomes interact with other organelles thus leading fusion or non-fusogenic contacts. And these varying localizations may result in its functional differences.
Since PLAC8 was identified 20 years ago, many studies have been performed to identify the characteristics and molecular functions of PLAC8 in cancer (Fig. 2) [40]. PLAC8 promotes the growth of tumor cells in prostate cancer cells [41] but significantly inhibits the growth of tumor cells in hepatocellular carcinoma [42]. This interesting phenomenon prompts us to explore the underlying mechanisms and regulatory network of PLAC8. Therefore, research on PLAC8 will help us to further understand the biological characteristics of tumors.
Timeline of PLAC8 research. A brief history of functional and pharmacological studies of PLAC8
Connections with cancer
As a key regulator of growth in different species, including fungi [43], plants [24, 44] and mammals [3, 30, 45, 46], PLAC8 participates in many important physiological activities in different contexts [31, 47,48,49]. Such as, the ratio of FAIM3:PLAC8 might be a diagnostic biomarker in sepsis [47]. And PLAC8 is related with septic shock [49]. To date, researchers have also found that PLAC8 acts as a tumor associated gene that is involved in many cancer processes (Fig. 3) [50,51,52,53,54,55]. We further discuss the various molecular functions of PLAC8 in cancer in our review.
Schematic overview of PLAC8 functions in cancer progression
Programed cell death
Programmed cell death, referring to apoptosis, autophagy, programmed necrosis and ferroptosis, may jointly decide the fate of malignant neoplasm cells [56,57,58]. These forms of programmed cell death balance cell death with cell survival, thus regulating cancer cell fate. Many oncogenes or tumor suppressor genes are linked with tumorigenesis through programmed cell death [59,60,61]. PLAC8, as an oncogene, promotes colorectal and prostate cancer cell growth [62,63,64]. Cancer growth is always accompanied by programmed cell death. As expected, PLAC8 regulates cell apoptosis in various cancers [65]. We found that PLAC8 inhibits breast cancer cell apoptosis, thus promoting cell proliferation [34]. PLAC8 decreases the sensitivity of lung adenocarcinoma cells to gefitinib-induced apoptosis by reducing the expression of cleaved caspase 3 and cleaved PARP [45]. The mRNA levels of PLAC8 are increased in stool, and that its increased expression correlates with colorectal cells relapse [63, 66]. PLAC8 is also upregulated in late-stage colorectal patient’s tissues and butyrate which produces microorganisms downregulated PLAC8 expression. And butyrate increased cleaved PARP fragment and then induced apoptosis in colorectal cells [62]. Exception of cancer cells, PLAC8 can also inhibits cell apoptosis of primary human and established rat fibroblasts via promoting the activation of MDM-2 and AKT1 and then inhibiting p53 [25]. Akt/MDM-2/p53 pathway serves an important role in the regulation of cell apoptosis [67]. And autophagy, is a process that delivers cytoplasmic components to the lysosomes which PLAC8 locates in [38], has opposing and context-dependent roles in cancer [68]. Autophagy induces pancreatic ductal adenocarcinoma cells growth [69]. Pancreatic ductal adenocarcinoma has signature oncogenic mutations of KRAS and the inactivation of p53 [70]. Additionally, in pancreatic ductal adenocarcinoma cell lines, PLAC8 is cooperatively induced in response to mutations in KRAS [71] and p53 [72] which are the two of the most commonly occurring mutations in cancer. And then PLAC8 promote pancreatic ductal adenocarcinoma cell lines autophagy thus promoting tumor formation [38]. The oncogenic role of PLAC8 in inducing the prosurvival function of autophagy protects cells from environmental stress and aids in the transformation of prostate epithelial cells during chronic exposure to cadmium [41]. We previously shown that PLAC8 collaborates with p62 to suppress autophagy in doxorubicin resistant breast cancer cells [36]. PLAC8 inhibits autophagy via the AKT/mTOR pathway in nasopharyngeal carcinoma cells [73]. In addition to cancer, PLAC8 also enhances autophagy in adult-onset Still’s disease [74] and promotes trophoblast cells autophagy though regulating autophagy-related markers, including LC3B I/II, ATG12 and Beclin-1 [75]. However, the relationship of PLAC8 with programmed necrosis and ferroptosis, which is a new form of cell death, is still unknown. We previously discussed that an interaction exists between ferroptosis and autophagy [76]. The crosstalk between autophagy and apoptosis regulates testicular injury induced by cadmium via PI3K and a mTOR-independent pathway [77]. Interestingly, PLAC8 regulates the PI3K pathway and interacts with AKT, which is an important kinase of the PI3K pathway [34, 42, 78]. These results strongly indicate that PLAC8 may be a core regulator in programmed cell death, affect different forms of cell death and decide cancer cell fate. This intriguing contrast in the effects of PLAC8 on cell fate in different cellular contexts presents attractive possibilities for the development of novel therapies for cancers.
Cancer stemness
Stem cells are a population of undifferentiated cells characterized by the ability of self-renewal, such as embryonic stem cells. Studies have shown that the expression of PLAC8 and several recognized stem cell markers (NANOG [79], SOX2 [80] and POU5F1 [81]) are commonly highly expressed in embryo development [82]. In POU5F1-null embryonic stem cells, PLAC8 is downregulated [83]. PLAC8 also may be upstream of KLF4 which is a stem cell marker [84] in triggering adipogenesis [51]. These studies suggest that PLAC8 may involve in stem cell progression vis interacting with stem cell markers. Consistant with stem cells, cancer stem cells (CSCs) have the potential to self-renew, and they often appear dormant and resist cancer treatments, such as radiation and chemotherapy, leading to cancer recurrence. Higher PLAC8 expression is found in the sphere-forming colorectal cancer cells than in colorectal cancer cells. And Id1 gene which can activate the Wnt/β-catenin and Shh signaling pathways promote PLAC8 expression and then maintains cell stemness in colorectal cancer [85]. In non-small cell lung cancer, PLAC8 promotes the levels of ALDH1A1 which is a putative marker for CSCs in numerous types of tumors [86,87,88]. Additionally, PLAC8 regulates the expression of POU5F1, thus increasing stemness during lung adenocarcinoma cell resistance to radiotherapy [89]. And our previous study showed that KLF4 regulates PLAC8 transcription in lung cancer cells [90]. These studies strongly indicates that the regulation loop between stem cell markers (POU5F1 and KLF4) and PLAC8 and the various roles of PLAC8 in cancer stemness. The precise association of PLAC8 with recognized stem cell markers still need further explored. Based on emerging evidence, PLAC8 may be a promising stemness related marker in tumor initiation and development.
Epithelial-mesenchymal transition
Epithelial–mesenchymal transition (EMT) is a cellular process in which cells lose their epithelial characteristics and acquire mesenchymal features that have been associated with metastasis [91]. Studies have shown that PLAC8 overexpression contributes to MAPK pathway activation and metastatic phenotypes [92] and that PLAC8 plays a role in the epithelial-mesenchymal transition [93] in different types of cancer. PLAC8 promotes trophoblast cell, non-small cell lung cancer cell, and clear cell renal cell carcinoma invasion and migration [17, 88, 94, 95]. However, PLAC8 inhibits oral squamous cell invasion [95]. PLAC8 reflects the expression of epithelial-mesenchymal related markers including E-cadherin, N-cadherin and vimentin thus involving epithelial-mesenchymal transition process. In breast cancer cells, embryonic kidney 293 T cells, colorectal cancer cells and nasopharyngeal carcinoma cells, PLAC8 downregulates the level of E-cadherin thus regulating cell migration and invasion [34, 35, 96, 97]. On the other hand, PLAC8 upregulates N-cadherin and vimentin levels in breast cancer and nasopharyngeal carcinoma cells [34, 73]. Interestingly, PLAC8 decreases E-cadherin expression but increases P-cadherin and vimentin expression; however, the level of N-cadherin is stable in colorectal cancer cells [33]. These studies demonstrate that the molecular function of PLAC8 varies in different contexts. The difference in cellular position may not be sufficient to explain this phenomenon, and in-depth research is needed in the future. In addition to cadherin family proteins, the abundant expression of PLAC8 in interstitial extravillous trophoblast cells promotes cell invasion and migration partially by upregulating the activation of RAC1 and CDC42 without change their expression [17]. PLAC8 not only promotes EMT progression but is also involved in cancer metastasis, such as bone metastasis in prostate cancer cells and lung metastasis in colorectal cancer cells in vivo [62, 64]. Taken together, PLAC8 may reflect epithelial-mesenchymal related genes thus involving EMT progression and cancer metastasis. Additionally, the expression of PLAC8 can predict of changes in EMT markers, including E-cadherin, N-cadherin and vimentin and be the hallmark of EMT progression.
Cancer immunity
PLAC8 exists in a variety of immune cells and the level of PLAC8 varies in different immune cells. PLAC8 is higher expressed by Th1 CD4 T-cells compared to Th2, Th17 and iTreg CD4 T-cells [22]. In addition, PLAC8 is relatively highly expressed in airway T helper 2 (Th2) cells which play a pathogenic role in allergies [98]. PLAC8 is robustly downregulated in CD39+ human regulatory T-cells [99]. In addition to being expressed in immune cells, PLAC8 also interacts with immune factors and regulates inflammation. For example, PLAC8 suppresses the production of the pro-inflammatory cytokines, IL-1b and IL-18, via enhancement of autophagy in adult-onset Still’s disease [74]. PLAC8 is important for suppressing IFNγ production by IL-12 stimulation in CD4 T-cell [22]. And CD4 T-cell expression of PLAC8 correlates with potent termination of Chlamydia replication and relative independence from IFNγ pretreatment of epithelial monolayers [100, 101]. And Chlamydia-specific CD8 T-cell clones do not express PLAC8 [102], but PLAC8 also promotes effector CD8 T-cell establishment through a T cell-intrinsic mechanism. In addition, PLAC8 is identified in placental functions, and PLAC8 is relatively higher in placentitis cells [103]. PLAC8 mRNA is also increased in the myometrium of adenomyosis patients, indicating the role of the immune response in the myometrium of women with adenomyosis [104]. These evidences suggest that PLAC8 may play an important role in immune system [31, 105, 106]. Determining factors that regulate PLAC8 expression in T cells may help to identify how it can be utilized therapeutically during T cell-driven inflammation, and the functions of PLAC8 in the immune system, especially in the regulation of different populations of immune cells, need to be explored further.
When referred to cancer immunity, PLAC8 is found to be most intensively expressed in the FXIII-A dim subgroup and helps to define three novel subpopulations in pediatric B-cell progenitor acute lymphoblastic leukemia [107]. And RNA sequencing data of clear cell renal cell carcinoma has shown that PLAC8 is mainly involved in immunity-related pathways [94]. With unbiased RNA sequence analysis, CXCL5, which is an inflammatory mediator, has been identified as one of the downstream targets of PLAC8 overexpression in osteosarcoma [92]. Gong et al. found that PLAC8 is abnormally overexpressed in gallbladder carcinoma cells and that its expression positively correlates with PD-L1 expression, which is the main checkpoint of the immune system [108]. However, time and more research will begin to address questions that how PLAC8 involves cancer immunity. While these findings were initially unexpected, PLAC8 is an immune-related gene and may be a targeting gene for immune reactions in cancer.
Drug resistance
In the ericoid mycorrhizal fungus, Oidiodendron maius, PLAC8-containing proteins have been reported to be involved in cadmium tolerance [28]. Additionally, specifically targeting PLAC8 may affect prostate carcinogenesis in humans, and PLAC8 activation may be used as a biomarker for the early detection of prostate cancer in cadmium-exposed populations [41]. These findings indicate that the expression of PLAC8 might be altered upon exposure to certain drugs. Drug resistance is one of the main reasons for the failure of tumor therapy, which greatly limits the choice and use of cancer drugs. Researchers have demonstrated that PLAC8 is related to multidrug resistance in various cancers. In nasopharyngeal carcinoma cells, knockout of PLAC8 radiosensitizes nasopharyngeal carcinoma cells by activating the PI3K/AKT/GSK3β pathway [78]. Our study found that overexpression of PLAC8 can promote tamoxifen resistance in breast cancer and that the expression of PLAC8 can be reduced by curcumin [96]. In addition to endocrine resistance, PLAC8 regulates RAC1 levels, and another study has reported that RAC1 promotes breast cancer chemoresistance by influencing DNA damage repair [17, 109]. These findings indicate that PLAC8 may predict multidrug resistance in breast cancer. In non-small cell lung cancer, overexpression of PLAC8 in parental cells markedly decreases osimertinib sensitivity [88]. Enhanced sensitivity to cisplatin treatment following silencing of PLAC8 in clear cell renal cell carcinoma cells suggests a potential therapeutic target of PLAC8 [94]. PLAC8 overexpression decreases sensitivity to gemcitabine and oxaliplatin in gallbladder carcinoma cells [108]. Overexpression of PLAC8 significantly decreases the sensitivity of lung adenocarcinoma to gefitinib [45]. Taken together, these results suggest that PLAC8 may predict drug resistance in various cancer cells and be a promising therapeutic target.
Other diseases
In addition to its important role in tumors, PLAC8 also participates in other disease processes, such as respiratory diseases and some infectious diseases [98, 102, 110]. For example, PLAC8 is upregulated in activated monocytes and in monocytes isolated from active ASD patients [74]. In addition, many studies have shown that PLAC8 is related to glucose metabolism [26]. However, animal models have shown that PLAC8 is expressed at different levels in F344-fa and F344-fa-nidd2 rats and is closely related to obesity and glucose loading [15]. The AIM3:PLAC8 ratio is a candidate biomarker that can be used to assist in the rapid diagnosis of CAP on ICU admission [111]. The study of PLAC8 in different systemic diseases in humans may help to further understand the function of this gene.
Overview of the PLAC8-regulated network
There is mounting evidence of the potential role of PLAC8-regulated network in cancer (Fig. 4) [104, 111, 112]. PLAC8 can be regulated at the transcriptional level. For example, PLAC8 is involved in pro-mesonephros regulation, and PAX2 regulates the transcription of PLAC8 [113]. PLAC8 is upregulated by IFNT [114], and the expression of PLAC8 is upregulated under hypoxia [17]. PLAC8 acts as a transcription factor involved in the expression of different genes. In CD4 T cells, PLAC8 suppresses IL-12-induced IFNγ production at the transcriptional level [22]. PLAC8 binds to the C/EBPβ promoter to induce its transcription [26]. PLAC8 activates the Akt/MDM-2 pathway, ultimately leading to an inability to upregulate p53. In addition, PLAC8 directly interacts with MDM-2 and Akt, thereby influencing the localization of both proteins [25]. In functional extravillous trophoblasts, PLAC8 colocalizes with p53 and regulates p53 expression at the posttranslational level [75]. In addition, the expression of PLAC8 can be reduced by curcumin in tamoxifen resistant breast cancer [96]. And butyrate reduced the expression of PLAC8 in colorectal cancer cells [62]. In acute myeloid leukemic cell lines, all-trans retinoic acid (ATRA) and phorbol 12-myristate 13-acetate (PMA) downregulate PLAC8 expression though PKCɛ-ERK2 signaling pathway [50]. As shown in Fig. 3, PLAC8 interacts with tumor-related genes both at the transcriptional and posttranscriptional levels, thereby playing a functional role in cancer progression.
Signaling pathways and genes controlling PLAC8 expression and its regulatory system. PLAC8 regulation is driven by different factors in both the nucleus and cytoplasm. It is important to point out that published mechanisms of PLAC8 regulation are not yet completely understood. Studies have shown that growth-related signaling pathways, such as the AKT, MAPK and TGF-β/Smad pathways, interact with PLAC8. Some drugs, such as curcumin and PAM, directly and indirectly affect PLAC8 levels. In addition, PLAC8, as a transcription factor, promotes C/EBPβ transcription and inhibits PU.1 transcription. The dashed lines depict mechanisms that are not completely understood. C/EBPβ, enhancer-binding protein β; ALDH1A1, aldehyde dehydrogenase 1 family member A1; CDC42, cell division control protein 42; POU5F1, POU Class 5 homeobox 1; RAC1, ras-related C3 botulinum toxin substrate 1; KLF4, Kruppel-like factor-4; PLAC8, placenta-specific gene 8; PU.1, Spi-1 proto-oncogene; CD98, ectonucleoside triphosphate diphosphohydrolase 1; ID1, inhibitor of differentiationId-1; PKCɛ, protein kinase C ɛ; ERK2, extracellular regulated protein kinases 2; c-Myc, cellular myelocytomatosis viral oncogene; CXCL5, C-X-C motif chemokine 5; DUSP6, dual specificity phosphatase 6; MDM-2, murine double minute 2; p53, tumor protein 53
Conclusion and perspectives
Our understanding of the molecular mechanisms of PLAC8 has expanded over the last decade, and this knowledge has been used to build better models that allow us to unravel the complicated role of the PLAC8 gene in human diseases. Furthermore, these studies have led to the identification of putative therapeutics to target PLAC8. While PLAC8 accumulates in most tumor cells, it tends to contribute to tumor progression by inducing tumorigenesis, immune reactions, chemoresistance and metastasis. As discussed above, PLAC8 has been identified in breast cancer, prostate cancer, lung cancer gallbladder cancer and nasopharyngeal cancer (Fig. 5). The molecular functions of PLAC8 in the brain, gastric carcinoma and osteocarcinoma remain unknown and need to be explored. Based on these studies, we suggest that PLAC8 may be a promising marker and predictor for clinical drug selection, immunotherapy response and tumor prognosis. The precise roles of PLAC8 in different cancers vary, and its underlying mechanisms should be determined in the future. In addition, the relative network related to PLAC8 is still not clear. Therefore, the mechanisms by which PLAC8 selects its downstream partners and is reflected by other genes may reveal new players and mechanisms by which PLAC8 orchestrates cancer cell behavior, thereby suggesting new targets for therapy. Another aspect that deserves attention is to understand the functional structure of each region of the PLAC8 protein, which will help to comprehend the related molecular mechanism of the protein. Further characterization of the PLAC8 protein in different cell types is paramount not only to enrich our understanding of this gene in normal physiology but also to enhance our ability to target it to reduce cancer progression. Thus, the precise roles of PLAC8 in different forms of programmed cancer death need to be discovered in the future.
Epidemiological data and functional evidence of PLAC8 in tumor types
Availability of data and materials
Not applicable.
References
Galaviz-Hernandez C, Stagg C, de Ridder G, Tanaka TS, Ko MSH, Schlessinger D, et al. Plac8 and Plac9, novel placental-enriched genes identified through microarray analysis. Gene. 2003;309(2):81–9. https://doi.org/10.1016/S0378-1119(03)00508-0.
Tanaka TS, Jaradat SA, Lim MK, et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci U S A. 2000;97(16):9127–32.
El-Sheikh Ali H, Scoggin K, Linhares Boakari Y, et al. Kinetics of placenta-specific 8 (PLAC8) in equine placenta during pregnancy and placentitis. Theriogenology. 2021;160:81–9. https://doi.org/10.1016/j.theriogenology.2020.10.041.
Lopera-Vasquez R, Hamdi M, Fernandez-Fuertes B, et al. Extracellular vesicles from BOEC in in vitro embryo development and quality. PLoS One. 2016;11(2):e0148083. https://doi.org/10.1371/journal.pone.0148083.
Machado GM, Caixeta ES, Lucci CM, Rumpf R, Franco MM, Dode MA. Post-hatching development of bovine embryos in vitro: the effects of tunnel preparation and gender. Zygote. 2012;20(2):123–34. https://doi.org/10.1017/S0967199411000086.
Machado GM, Ferreira AR, Guardieiro MM, Bastos MR, Carvalho JO, Lucci CM, et al. Morphology, sex ratio and gene expression of day 14 in vivo and in vitro bovine embryos. Reprod Fertil Dev. 2013;25(4):600–8. https://doi.org/10.1071/RD11282.
Hoelker M, Rings F, Lund Q, Ghanem N, Phatsara C, Griese J, et al. Effect of the microenvironment and embryo density on developmental characteristics and gene expression profile of bovine preimplantative embryos cultured in vitro. Reproduction. 2009;137(3):415–25. https://doi.org/10.1530/REP-08-0370.
Gomez E, Caamano JN, Bermejo-Alvarez P, et al. Gene expression in early expanded parthenogenetic and in vitro fertilized bovine blastocysts. J Reprod Dev. 2009;55(6):607–14.
El-Sayed A, Hoelker M, Rings F, et al. Large-scale transcriptional analysis of bovine embryo biopsies in relation to pregnancy success after transfer to recipients. Physiol Genomics. 2006;28(1):84–96. https://doi.org/10.1152/physiolgenomics.00111.2006.
Gomez E, Gutierrez-Adan A, Diez C, et al. Biological differences between in vitro produced bovine embryos and parthenotes. Reproduction. 2009;137(2):285–95. https://doi.org/10.1530/REP-08-0220.
Lazzari G, Colleoni S, Duchi R, Galli A, Houghton FD, Galli C. Embryonic genotype and inbreeding affect preimplantation development in cattle. Reproduction. 2011;141(5):625–32. https://doi.org/10.1530/REP-10-0282.
Bermejo-Alvarez P, Lonergan P, Rath D, Gutierrez-Adan A, Rizos D. Developmental kinetics and gene expression in male and female bovine embryos produced in vitro with sex-sorted spermatozoa. Reprod Fertil Dev. 2010;22(2):426–36. https://doi.org/10.1071/RD09142.
Sultana N, Islam S, Juhasz A, Yang R, She M, Alhabbar Z, et al. Transcriptomic study for identification of major nitrogen stress responsive genes in Australian bread wheat cultivars. Front Genet. 2020;11:583785. https://doi.org/10.3389/fgene.2020.583785.
Lee H, Kim JI, Park JS, Roh JI, Lee J, Kang BC, et al. CRISPR/Cas9-mediated generation of a Plac8 knockout mouse model. Lab Anim Res. 2018;34(4):279–87. https://doi.org/10.5625/lar.2018.34.4.279.
Sasaki D, Kotoh J, Watadani R, Matsumoto K. New animal models reveal that coenzyme Q2 (Coq2) and placenta-specific 8 (Plac8) are candidate genes for the onset of type 2 diabetes associated with obesity in rats. Mamm Genome. 2015;26(11–12):619–29. https://doi.org/10.1007/s00335-015-9597-4.
Cebrian-Serrano A, Salvador I, García-Roselló E, Pericuesta E, Pérez-Cerezales S, Gutierrez-Adán A, et al. Effect of the bovine Oviductal fluid onIn VitroFertilization, development and gene expression ofIn vitro-produced bovine blastocysts. Reprod Domest Anim. 2013;48(2):331–8. https://doi.org/10.1111/j.1439-0531.2012.02157.x.
Chang WL, Liu YW, Dang YL, et al. PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration. Development. 2018;145(2):dev148932. https://doi.org/10.1242/dev.148932.
Suwik K, Sinderewicz E, Boruszewska D, et al. mRNA expression and role of PPARgamma and PPARdelta in bovine preimplantation embryos depending on the quality and developmental stage. Animals (Basel). 2020;10(12):2358. https://doi.org/10.3390/ani10122358.
Korzekwa AJ, Kotlarczyk AM, Szczepanska AA, Grzyb M, Siergiej A, Woclawek-Potocka I. Antioxidative potential of red deer embryos depends on reproductive stage of hind as a oocyte donor. Animals (Basel). 2020;10(7):1190. https://doi.org/10.3390/ani10071190.
Blue EK, Sheehan BM, Nuss ZV, et al. Epigenetic regulation of placenta-specific 8 contributes to altered function of endothelial Colony-forming cells exposed to intrauterine gestational diabetes mellitus. Diabetes. 2015;64(7):2664–75. https://doi.org/10.2337/db14-1709.
Machado GM, Ferreira AR, Pivato I, Fidelis A, Spricigo JF, Paulini F, et al. Post-hatching development of in vitro bovine embryos from day 7 to 14 in vivo versus in vitro. Mol Reprod Dev. 2013;80(11):936–47. https://doi.org/10.1002/mrd.22230.
Slade CD, Reagin KL, Lakshmanan HG, Klonowski KD, Watford WT. Placenta-specific 8 limits IFNgamma production by CD4 T cells in vitro and promotes establishment of influenza-specific CD8 T cells in vivo. PLoS One. 2020;15(7):e0235706. https://doi.org/10.1371/journal.pone.0235706.
Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci U S A. 2000;97(16):9127–32. https://doi.org/10.1073/pnas.97.16.9127.
Libault M, Stacey G. Evolution of FW2.2-like (FWL) and PLAC8 genes in eukaryotes. Plant Signal Behav. 2010;5(10):1226–8. https://doi.org/10.4161/psb.5.10.12808.
Rogulski K, Li Y, Rothermund K, Pu L, Watkins S, Yi F, et al. Onzin, a c-Myc-repressed target, promotes survival and transformation by modulating the Akt-Mdm2-p53 pathway. Oncogene. 2005;24(51):7524–41. https://doi.org/10.1038/sj.onc.1208897.
Jimenez-Preitner M, Berney X, Uldry M, Vitali A, Cinti S, Ledford JG, et al. Plac8 is an inducer of C/EBPbeta required for brown fat differentiation, thermoregulation, and control of body weight. Cell Metab. 2011;14(5):658–70. https://doi.org/10.1016/j.cmet.2011.08.008.
Nakano M, Iida K, Nyunoya H, Iida H. Determination of structural regions important for ca (2+) uptake activity in Arabidopsis MCA1 and MCA2 expressed in yeast. Plant Cell Physiol. 2011;52(11):1915–30. https://doi.org/10.1093/pcp/pcr131.
Di Vietro L, Daghino S, Abbà S, Perotto S. Gene expression and role in cadmium tolerance of two PLAC8-containing proteins identified in the ericoid mycorrhizal fungus Oidiodendron maius. Fungal Biol. 2014;118(8):695–703. https://doi.org/10.1016/j.funbio.2014.04.011.
Song WY, Hortensteiner S, Tomioka R, Lee Y, Martinoia E. Common functions or only phylogenetically related? The large family of PLAC8 motif-containing/PCR genes. Mol Cells. 2011;31(1):1–7. https://doi.org/10.1007/s10059-011-0024-8.
Cabreira-Cagliari C. Dias NdC, Bohn B, et al. revising the PLAC8 gene family: from a central role in differentiation, proliferation, and apoptosis in mammals to a multifunctional role in plants. Genome. 2018;61(12):857–65. https://doi.org/10.1139/gen-2018-0035.
Pang Q, Gao L, Bai Y, Deng H, Han Y, Hu W, et al. Identification and characterization of a novel multifunctional placenta specific protein 8 in Dugesia japonica. Gene. 2017;613:1–9. https://doi.org/10.1016/j.gene.2017.02.024.
Li M, Liu D, Wang L, Wang W, Wang A, Yao Y. Expression of placenta-specific 8 in human oocytes, embryos, and models of in vitro implantation. Fertil Steril. 2016;106(3):781–9 e782. https://doi.org/10.1016/j.fertnstert.2016.05.018.
Li C, Ma H, Wang Y, Cao Z, Graves-Deal R, Powell AE, et al. Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. J Clin Invest. 2014;124(5):2172–87. https://doi.org/10.1172/JCI71103.
Mao M, Chen Y, Jia Y, Yang J, Wei Q, Li Z, et al. PLCA8 suppresses breast cancer apoptosis by activating the PI3k/AKT/NF-kappaB pathway. J Cell Mol Med. 2019;23(10):6930–41. https://doi.org/10.1111/jcmm.14578.
Huang M-L, Zou Y, Yang R, Jiang Y, Sheng JF, Han JB, et al. Placenta specific 8 gene induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via the TGF-β/Smad pathway. Exp Cell Res. 2019;374(1):172–80. https://doi.org/10.1016/j.yexcr.2018.11.021.
Chen Y, Jia Y, Mao M, et al. PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer. J Cell Mol Med. 2021.
Kaistha BP, Lorenz H, Schmidt H, Sipos B, Pawlak M, Gierke B, et al. PLAC8 localizes to the inner plasma membrane of pancreatic Cancer cells and regulates cell growth and disease progression through critical cell-cycle regulatory pathways. Cancer Res. 2016;76(1):96–107. https://doi.org/10.1158/0008-5472.CAN-15-0216.
Kinsey C, Balakrishnan V, O'Dell MR, et al. Plac8 links oncogenic mutations to regulation of autophagy and is critical to pancreatic cancer progression. Cell Rep. 2014;7(4):1143–55. https://doi.org/10.1016/j.celrep.2014.03.061.
Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2020;21(2):101–18. https://doi.org/10.1038/s41580-019-0185-4.
Grate LR. Many accurate small-discriminatory feature subsets exist in microarray transcript data: biomarker discovery. BMC Bioinformatics. 2005;6(1):97. https://doi.org/10.1186/1471-2105-6-97.
Kolluru V, Pal D, Papu John AMS, Ankem MK, Freedman JH, Damodaran C. Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis. Cancer Lett. 2017;408:121–9. https://doi.org/10.1016/j.canlet.2017.08.023.
Zou L, Chai J, Gao Y, Guan J, Liu Q, Du JJ. Down-regulated PLAC8 promotes hepatocellular carcinoma cell proliferation by enhancing PI3K/Akt/GSK3beta/Wnt/beta-catenin signaling. Biomed Pharmacother. 2016;84:139–46. https://doi.org/10.1016/j.biopha.2016.09.015.
Daghino S, Di Vietro L, Petiti L, et al. Yeast expression of mammalian Onzin and fungal FCR1 suggests ancestral functions of PLAC8 proteins in mitochondrial metabolism and DNA repair. Sci Rep. 2019;9(1):6629. https://doi.org/10.1038/s41598-019-43136-3.
Guo M, Rupe MA, Dieter JA, Zou J, Spielbauer D, Duncan KE, et al. Cell number Regulator1 affects plant and organ size in maize: implications for crop yield enhancement and heterosis. Plant Cell. 2010;22(4):1057–73. https://doi.org/10.1105/tpc.109.073676.
Zeng X, Liu Q, Yang Y, Jia W, Li S, He D, et al. Placenta-specific protein 8 promotes the proliferation of lung adenocarcinoma PC-9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway. Oncol Lett. 2019;18(5):5621–7. https://doi.org/10.3892/ol.2019.10911.
Mansouri-Attia N, Aubert J, Reinaud P, Giraud-Delville C, Taghouti G, Galio L, et al. Gene expression profiles of bovine caruncular and intercaruncular endometrium at implantation. Physiol Genomics. 2009;39(1):14–27. https://doi.org/10.1152/physiolgenomics.90404.2008.
Sweeney TE, Khatri P. Comprehensive validation of the FAIM3:PLAC8 ratio in time-matched public gene expression data. Am J Respir Crit Care Med. 2015;192(10):1260–1.
Sweeney TE, Khatri P. Benchmarking Sepsis gene expression diagnostics using public data. Crit Care Med. 2017;45(1):1–10. https://doi.org/10.1097/CCM.0000000000002021.
Tang Y, Yang X, Shu H, Yu Y, Pan S, Xu J, et al. Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury. Hereditas. 2021;158(1):13. https://doi.org/10.1186/s41065-021-00176-y.
Wu SF, Huang Y, Hou JK, Yuan TT, Zhou CX, Zhang J, et al. The downregulation of onzin expression by PKCepsilon-ERK2 signaling and its potential role in AML cell differentiation. Leukemia. 2010;24(3):544–51. https://doi.org/10.1038/leu.2009.280.
Jimenez-Preitner M, Berney X, Thorens B. Plac8 is required for white adipocyte differentiation in vitro and cell number control in vivo. PLoS One. 2012;7(11):e48767. https://doi.org/10.1371/journal.pone.0048767.
Reddy RB, Bhat AR, James BL, Govindan SV, Mathew R, DR R, et al. Meta-analyses of microarray datasets identifies ANO1 and FADD as prognostic markers of head and neck Cancer. PLoS One. 2016;11(1):e0147409. https://doi.org/10.1371/journal.pone.0147409.
Li H, Wang X, Fang Y, Huo Z, Lu X, Zhan X, et al. Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma. Oncotarget. 2017;8(32):52571–83. https://doi.org/10.18632/oncotarget.16732.
Tatura M, Schmidt H, Haijat M, Stark M, Rinke A, Diels R, et al. Placenta-specific 8 is overexpressed and regulates cell proliferation in low-grade human pancreatic neuroendocrine tumors. Neuroendocrinology. 2020;110(1–2):23–34. https://doi.org/10.1159/000500541.
Hung CS, Wang YC, Guo JW, Yang RN, Lee CL, Shen MH, et al. Expression pattern of placenta specific 8 and keratin 20 in different types of gastrointestinal cancer. Mol Med Rep. 2020;21(2):659–66. https://doi.org/10.3892/mmr.2019.10871.
Dixon Scott J, Lemberg Kathryn M, Lamprecht Michael R, et al. Ferroptosis: an Iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72. https://doi.org/10.1016/j.cell.2012.03.042.
Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 2009;16(1):3–11. https://doi.org/10.1038/cdd.2008.150.
D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019;43(6):582–92. https://doi.org/10.1002/cbin.11137.
Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29(5):347–64. https://doi.org/10.1038/s41422-019-0164-5.
Van Opdenbosch N, Lamkanfi M. Caspases in cell death, inflammation, and disease. Immunity. 2019;50(6):1352–64. https://doi.org/10.1016/j.immuni.2019.05.020.
Newton K, Wickliffe KE, Maltzman A, Dugger DL, Reja R, Zhang Y, et al. Activity of caspase-8 determines plasticity between cell death pathways. Nature. 2019;575(7784):679–82. https://doi.org/10.1038/s41586-019-1752-8.
Huang CC, Shen MH, Chen SK, Yang SH, Liu CY, Guo JW, et al. Gut butyrate-producing organisms correlate to placenta specific 8 protein: importance to colorectal cancer progression. J Adv Res. 2020;22:7–20. https://doi.org/10.1016/j.jare.2019.11.005.
Lee CL, Huang CJ, Yang SH, Chang CC, Huang CC, Chien CC, et al. Discovery of genes from feces correlated with colorectal cancer progression. Oncol Lett. 2016;12(5):3378–84. https://doi.org/10.3892/ol.2016.5069.
Uehara H, Takahashi T, Izumi K. Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. Int J Oncol. 2013;43(2):365–74. https://doi.org/10.3892/ijo.2013.1954.
Mourtada-Maarabouni M, Watson D, Munir M, Farzaneh F. T. Williams G. apoptosis suppression by candidate oncogene PLAC8 is reversed in other cell types. Curr Cancer Drug Targets. 2013;13(1):80–91. https://doi.org/10.2174/156800913804486584.
Chang CC, Huang CC, Yang SH, Chien CC, Lee CL, Huang CJ. Data on clinical significance of GAS2 in colorectal cancer cells. Data Brief. 2016;8:82–6. https://doi.org/10.1016/j.dib.2016.05.010.
Xu W, Gao L, Li T, Zheng J, Shao A, Zhang J. Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects against neuronal apoptosis via activation of Akt/MDM2/p53 signaling pathway in a rat model of intracerebral hemorrhage. Front Mol Neurosci. 2018;11:176. https://doi.org/10.3389/fnmol.2018.00176.
Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017;17(9):528–42. https://doi.org/10.1038/nrc.2017.53.
Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25(7):717–29. https://doi.org/10.1101/gad.2016111.
Ying H, Dey P, Yao W, Kimmelman AC, Draetta GF, Maitra A, et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2016;30(4):355–85. https://doi.org/10.1101/gad.275776.115.
Prior IA, Hood FE, Hartley JL. The frequency of Ras mutations in Cancer. Cancer Res. 2020;80(14):2969–74. https://doi.org/10.1158/0008-5472.CAN-19-3682.
Levine AJ. p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer. 2020;20(8):471–80. https://doi.org/10.1038/s41568-020-0262-1.
Huang ML, Qi CL, Zou Y, et al. Plac8-mediated autophagy regulates nasopharyngeal carcinoma cell function via AKT/mTOR pathway. J Cell Mol Med. 2020;24(14):7778–88.
Segawa S, Kondo Y, Nakai Y, Iizuka A, Kaneko S, Yokosawa M, et al. Placenta specific 8 suppresses IL-18 production through regulation of autophagy and is associated with adult still disease. J Immunol. 2018;201(12):3534–45. https://doi.org/10.4049/jimmunol.1800667.
Feng X, Wei Z, Tao X, et al. PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells. FASEB J. 2021;35(3):e21351. https://doi.org/10.1096/fj.202002075RR.
Zhou Y, Shen Y, Chen C, Sui X, Yang J, Wang L, et al. The crosstalk between autophagy and ferroptosis: what can we learn to target drug resistance in cancer? Cancer Biol Med. 2019;16(4):630–46. https://doi.org/10.20892/j.issn.2095-3941.2019.0158.
Wang M, Wang XF, Li YM, Chen N, Fan Y, Huang WK, et al. Cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by cadmium via PI3K with mTOR-independent pathway. Cell Death Dis. 2020;11(1):46. https://doi.org/10.1038/s41419-020-2246-1.
Yang R, Tao ZZ, Huang ML, Zheng YF, Dai MY, Zou Y, et al. Knockout of the placenta specific 8 gene radiosensitizes nasopharyngeal carcinoma cells by activating the PI3K/AKT/GSK3beta pathway. Am J Transl Res. 2018;10(2):455–64.
Pan G, Thomson JA. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res. 2007;17(1):42–9. https://doi.org/10.1038/sj.cr.7310125.
Schaefer T, Lengerke C. SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond. Oncogene. 2020;39(2):278–92. https://doi.org/10.1038/s41388-019-0997-x.
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122(6):947–56. https://doi.org/10.1016/j.cell.2005.08.020.
Sugimura S, Kobayashi S, Hashiyada Y, Ohtake M, Kaneda M, Yamanouchi T, et al. Follicular growth-stimulated cows provide favorable oocytes for producing cloned embryos. Cell Reprogram. 2012;14(1):29–37. https://doi.org/10.1089/cell.2011.0060.
Fogarty NME, McCarthy A, Snijders KE, Powell BE, Kubikova N, Blakeley P, et al. Genome editing reveals a role for OCT4 in human embryogenesis. Nature. 2017;550(7674):67–73. https://doi.org/10.1038/nature24033.
Yin M, Zhou HJ, Lin C, et al. CD34+KLF4+ stromal stem cells contribute to endometrial regeneration and repair. Cell Rep. 2019;27(9):2709–2724.e2703.
Sun Y, Lai X, Yu Y, Li J, Cao L, Lin W, et al. Inhibitor of DNA binding 1 (Id1) mediates stemness of colorectal cancer cells through the Id1-c-Myc-PLAC8 axis via the Wnt/β-catenin and Shh signaling pathways</p>. Cancer Manag Res. 2019;11:6855–69. https://doi.org/10.2147/CMAR.S207167.
Wang Q, Jiang J, Ying G, et al. Tamoxifen enhances stemness and promotes metastasis of ERalpha36(+) breast cancer by upregulating ALDH1A1 in cancer cells. Cell Res. 2018;28(3):336–58.
Mori Y, Yamawaki K, Ishiguro T, Yoshihara K, Ueda H, Sato A, et al. ALDH-dependent glycolytic activation mediates Stemness and paclitaxel resistance in patient-derived spheroid models of uterine endometrial Cancer. Stem Cell Rep. 2019;13(4):730–46. https://doi.org/10.1016/j.stemcr.2019.08.015.
Fei X, Wang G, Shen H, Gu X. Placenta-specific 8 is a potential novel target for osimertinib resistance in non-small cell lung cancer. Oncol Lett. 2019;18(1):955–61. https://doi.org/10.3892/ol.2019.10344.
Jin Z, Guan L, Xiang GM, Gao BA. Radiation resistance of the lung adenocarcinoma is related to the AKT-Onzin-POU5F1 axis. Biochem Biophys Res Commun. 2018;499(3):538–43. https://doi.org/10.1016/j.bbrc.2018.03.185.
Jia Y, Ying X, Zhou J, Chen Y, Luo X, Xie S, et al. The novel KLF4/PLAC8 signaling pathway regulates lung cancer growth. Cell Death Dis. 2018;9(6):603. https://doi.org/10.1038/s41419-018-0580-3.
Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29(3):212–26. https://doi.org/10.1016/j.tcb.2018.12.001.
Zhang Y, Hu Q, Li G, Li L, Liang S, Zhang Y, et al. ONZIN upregulation by mutant p53 contributes to osteosarcoma metastasis through the CXCL5-MAPK sign9aling pathway. Cell Physiol Biochem. 2018;48(3):1099–111. https://doi.org/10.1159/000491976.
Qi C, Hong L, Cheng Z, Yin Q. Identification of metastasis-associated genes in colorectal cancer using metaDE and survival analysis. Oncol Lett. 2016;11(1):568–74. https://doi.org/10.3892/ol.2015.3956.
Shi L, Xiao L, Heng B, Mo S, Chen W, Su Z. Overexpression of placenta specific 8 is associated with malignant progression and poor prognosis of clear cell renal cell carcinoma. Int Urol Nephrol. 2017;49(7):1165–76. https://doi.org/10.1007/s11255-017-1578-y.
Wu J, Wang X, Shang A, Vella G, Sun Z, Ji P, et al. PLAC8 inhibits oral squamous cell carcinogenesis and epithelial-mesenchymal transition via the Wnt/beta-catenin and PI3K/Akt/GSK3beta signaling pathways. Oncol Lett. 2020;20(5):128. https://doi.org/10.3892/ol.2020.11989.
Mao M, Hu D, Yang J, Chen Y, Zhang X, Shen J, et al. Regulation of tamoxifen sensitivity by the PLAC8/MAPK pathway axis is antagonized by curcumin-induced protein stability change. J Mol Med. 2021;99(6):845–58. https://doi.org/10.1007/s00109-021-02047-5.
Qin X-H, Wang H-X, Ma L, Shen J, Liu Q-H, Xue L. Knockout of the placenta specific 8 gene affects the proliferation and migration of human embryonic kidney 293T cell. Cell Biochem Biophys. 2019;78(1):55–64. https://doi.org/10.1007/s12013-019-00893-2.
Tibbitt CA, Stark JM, Martens L, Ma J, Mold JE, Deswarte K, et al. Single-cell RNA sequencing of the T helper cell response to house dust mites defines a distinct gene expression signature in airway Th2 cells. Immunity. 2019;51(1):169–184.e5. https://doi.org/10.1016/j.immuni.2019.05.014.
Gerner MC, Ziegler LS, Schmidt RLJ, Krenn M, Zimprich F, Uyanik-Ünal K, et al. The TGF-b/SOX4 axis and ROS-driven autophagy co-mediate CD39 expression in regulatory T-cells. FASEB J. 2020;34(6):8367–84. https://doi.org/10.1096/fj.201902664.
Johnson RM, Kerr MS, Slaven JE. Plac8-dependent and inducible NO synthase-dependent mechanisms clear Chlamydia muridarum infections from the genital tract. J Immunol. 2012;188(4):1896–904. https://doi.org/10.4049/jimmunol.1102764.
Johnson RM, Kerr MS, Slaven JE. Perforin is detrimental to controlling [corrected] C. muridarum replication in vitro, but not in vivo. PLoS One. 2013;8(5):e63340.
Johnson RM, Kerr MS, Slaven JE. An atypical CD8 T-cell response to Chlamydia muridarum genital tract infections includes T cells that produce interleukin-13. Immunology. 2014;142(2):248–57. https://doi.org/10.1111/imm.12248.
El-Sheikh Ali H, Dini P, Scoggin K, et al. Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis†. Biol Reprod. 2021;104(3):638–56. https://doi.org/10.1093/biolre/ioaa209.
Zhai J, Li S, Sen S, et al. m (6) A RNA methylation regulators contribute to eutopic endometrium and myometrium dysfunction in adenomyosis. Front Genet. 2020;11:716.
McHugh L, Seldon TA, Brandon RA, Kirk JT, Rapisarda A, Sutherland AJ, et al. A molecular host response assay to discriminate between Sepsis and infection-negative systemic inflammation in critically ill patients: discovery and validation in independent cohorts. PLoS Med. 2015;12(12):e1001916. https://doi.org/10.1371/journal.pmed.1001916.
Verboom DM, Koster-Brouwer ME, Varkila MRJ, Bonten MJM, Cremer OL. Profile of the SeptiCyte™ LAB gene expression assay to diagnose infection in critically ill patients. Expert Rev Mol Diagn. 2019;19(2):95–108. https://doi.org/10.1080/14737159.2019.1567333.
Gyurina K, Karai B, Ujfalusi A, et al. Coagulation FXIII-A protein expression defines three novel sub-populations in pediatric B-cell progenitor acute lymphoblastic leukemia characterized by distinct gene expression signatures. Front Oncol. 2019;9:1063. https://doi.org/10.3389/fonc.2019.01063.
Gong K, Gong Z-J, Lu P-X, Ni XL, Shen S, Liu H, et al. PLAC8 overexpression correlates with PD-L1 upregulation and acquired resistance to chemotherapies in gallbladder carcinoma. Biochem Biophys Res Commun. 2019;516(3):983–90. https://doi.org/10.1016/j.bbrc.2019.06.121.
Li Q, Qin T, Bi Z, Hong H, Ding L, Chen J, et al. Rac1 activates non-oxidative pentose phosphate pathway to induce chemoresistance of breast cancer. Nat Commun. 2020;11(1):1456. https://doi.org/10.1038/s41467-020-15308-7.
Ziegler A, Marti E, Summerfield A, Baumann A. Identification and characterization of equine blood plasmacytoid dendritic cells. Dev Comp Immunol. 2016;65:352–7. https://doi.org/10.1016/j.dci.2016.08.005.
Scicluna BP, Klein Klouwenberg PM, van Vught LA, et al. A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission. Am J Respir Crit Care Med. 2015;192(7):826–35. https://doi.org/10.1164/rccm.201502-0355OC.
Y-y M, Liu J, Zhu J, et al. The effect of botulinum toxin type a on expression profiling of long noncoding RNAs in human dermal fibroblasts. BioMed Res Int. 2017;2017:1–13.
Boualia SK, Gaitan Y, Tremblay M, Sharma R, Cardin J, Kania A, et al. A core transcriptional network composed of Pax2/8, Gata3 and Lim1 regulates key players of pro/mesonephros morphogenesis. Dev Biol. 2013;382(2):555–66. https://doi.org/10.1016/j.ydbio.2013.07.028.
Cheng Z, Chauhan L, Barry AT, Abudureyimu A, Oguejiofor CF, Chen X, et al. Acute bovine viral diarrhea virus infection inhibits expression of interferon tau-stimulated genes in bovine endometrium. Biol Reprod. 2017;96(6):1142–53. https://doi.org/10.1093/biolre/iox056.
Acknowledgements
Not applicable.
Funding
The work was supported by the National Natural Science Foundation of China (No. 81972453 and No. 81972597), Zhejiang Provincial Natural Science Foundation of China (under Grant Nos. LY19H160055, LY19H160059, LY18H160005, and LY20H160026), and Zhejiang Provincial Medical and Health Science and Technology (Youth Talent Program) Project No. 2021RC016.
Author information
Authors and Affiliations
Contributions
MMS, CYF, JZC and WLB designed the review. MMS and CYF researched the literature and drafted the manuscript. YJJ, XL, CYX, JSW, LZQ, CC, and XZ edited the manuscript. All authors approved the final version of the manuscript.
Corresponding authors
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Mao, M., Cheng, Y., Yang, J. et al. Multifaced roles of PLAC8 in cancer. Biomark Res 9, 73 (2021). https://doi.org/10.1186/s40364-021-00329-1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s40364-021-00329-1