Abstract
Ovarian cancer seriously threatens the health of women. LncRNA CRNDE is known to be upregulated in ovarian cancer. However, the mechanism by which CRNDE regulates the progress of ovarian cancer is largely unknown. MTT assay was applied to measure the cell viability. Colony formation assay was used to measure the cell proliferation. Cell migration was tested by wound healing, and Transwell assay was performed to detect cell invasion. In addition, the expression of miR-423-5p, CRNDE and FSCN1 were detected by RT-qPCR and western blotting, respectively. Meanwhile, dual-luciferase reporter assay and RIP assay were performed to explore the correlation between miR-423-5p and CRNDE (or FSCN1). CRNDE and FSCN1 were upregulated in ovarian cancer cells (SKOV3, CAOV-3, IGROV1, A2780 and C13K), while miR-423-5p was downregulated. Moreover, silencing of FSCN1/CRNDE significantly decreased proliferation, migration and invasion of ovarian cancer cells (SKOV3 and CI3K) via suppressing MMP-2 and MMP-9. In addition, CRNDE could sponge miR-423-5p, and FSCN1 was confirmed to be the direct target of miR-423-5p. Furthermore, CRNDE knockdown-induced inhibition of FSCN1 was notably reversed by miR-423-5p downregulation. Knockdown of CRNDE inhibited cell proliferation, migration and invasion of ovarian cancer via miR-423-5p/FSCN1 axis. Thus, CRNDE may serve a new target for ovarian cancer.
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Abbreviations
- EOC:
-
Epithelial ovarian carcinoma
- EMT:
-
Epithelial-mesenchymal transition
- FSCN1:
-
Fascin-1
- FBS:
-
Fetal bovine serum
- Mut:
-
Mutant type
- MMP-2:
-
Matrix metalloproteinase-2
- MMP-9:
-
Matrix metalloproteinase-9
- WT:
-
Wild type
- RIP:
-
RNA immunoprecipitation
References
Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177:1053–1064. https://doi.org/10.2353/ajpath.2010.100105
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90. https://doi.org/10.3322/caac.20107
Karst AM, Drapkin R (2010) Ovarian cancer pathogenesis: a model in evolution. J Oncol 2010:932371. https://doi.org/10.1155/2010/932371
Reid BM, Permuth JB, Sellers TA (2017) Epidemiology of ovarian cancer: a review. Cancer Biol Med 14:9–32. https://doi.org/10.20892/j.issn.2095-3941.2016.0084
Lheureux S, Gourley C, Vergote I, Oza AM (2019) Epithelial ovarian cancer. The Lancet 393:1240–1253. https://doi.org/10.1016/s0140-6736(18)32552-2
Doherty JA, Peres LC, Wang C, Way GP, Greene CS, Schildkraut JM (2017) Challenges and opportunities in studying the epidemiology of ovarian cancer subtypes. Curr Epidemiol Rep 4:211–220. https://doi.org/10.1007/s40471-017-0115-y
Kiesslich T, Pichler M, Neureiter D (2013) Epigenetic control of epithelial-mesenchymal-transition in human cancer. Mol Clin Oncol 1:3–11. https://doi.org/10.3892/mco.2012.28
Meng F, Wu G (2012) The rejuvenated scenario of epithelial-mesenchymal transition (EMT) and cancer metastasis. Cancer Metastasis Rev 31:455–467. https://doi.org/10.1007/s10555-012-9379-3
Lars C, Hanker TK, Holtrich U, Graeser M, Becker S, Er JR, Gevensleben H, Rody A (2013) Prognostic impact of Fascin-1 (FSCN1) in epithelial ovarian cancer. Anticancer Res 33:371–378
Hashimoto Y, Skacel M, Adams JC (2005) Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol 37:1787–1804. https://doi.org/10.1016/j.biocel.2005.05.004
Al-Alwan M, Olabi S, Ghebeh H, Barhoush E, Tulbah A, Al-Tweigeri T, Ajarim D, Adra C (2011) Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS ONE 6:e27339. https://doi.org/10.1371/journal.pone.0027339
Winder SJ, Ayscough KR (2005) Actin-binding proteins. J Cell Sci 118:651–654. https://doi.org/10.1242/jcs.01670
Li J, Zhang S, Pei M, Wu L, Liu Y, Li H, Lu J, Li X (2018) FSCN1 Promotes epithelial-mesenchymal transition through increasing snail1 in ovarian cancer cells. Cell Physiol Biochem 49:1766–1777. https://doi.org/10.1159/000493622
Chen W, Bian H, Xie X, Yang X, Bi B, Li C, Zhang Y, Zhu Q, Song J, Qin C, Qi J (2020) Negative feedback loop of ERK/CREB/miR-212-3p inhibits HBeAg-induced macrophage activation. J Cell Mol Med. https://doi.org/10.1111/jcmm.15723
Tang R, Wang J, Zhou M, Lan Y, Jiang L, Price M, Yue B, Li D, Fan Z (2020) Comprehensive analysis of lncRNA and mRNA expression changes in Tibetan chicken lung tissue between three developmental stages. Anim Genet. https://doi.org/10.1111/age.12990
Wang D, Xing N, Yang T, Liu J, Zhao H, He J, Ai Y, Yang J (2020) Exosomal lncRNA H19 promotes the progression of hepatocellular carcinoma treated with Propofol via miR-520a-3p/LIMK1 axis. Cancer Med. https://doi.org/10.1002/cam4.3313
Li Y, Hou CZ, Dong YL, Zhu L, Xu H (2020) Long noncoding RNA LINP1 promoted proliferation and invasion of ovarian cancer via inhibiting KLF6. Eur Rev Med Pharmacol Sci 24:7918. https://doi.org/10.26355/eurrev_202008_22452
He Y, Wei L, Zhang S, Liu H, Fang F, Li Y (2020) LncRNA PLAC2 positively regulates CDK2 to promote ovarian carcinoma cell proliferation. Cancer Manag Res 12:5713–5720. https://doi.org/10.2147/CMAR.S242781
Yan H, Li H, Silva MA, Guan Y, Yang L, Zhu L, Zhang Z, Li G, Ren C (2019) LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer. J Exp Clin Cancer Res 38:356. https://doi.org/10.1186/s13046-019-1356-z
You Q, Shi HY, Gong CF, Tian XY, Li S (2019) Long non-coding RNA DLX6-AS1 acts as an oncogene by targeting miR-613 in ovarian cancer. Eur Rev Med Pharmacol Sci 23:6429–6435. https://doi.org/10.26355/eurrev_201908_18524
Luo X, Tu T, Zhong Y, Xu S, Chen X, Chen L, Yang F (2021) ceRNA network analysis shows that lncRNA CRNDE promotes progression of glioblastoma through sponge mir-9-5p. Front Genet 12:617350. https://doi.org/10.3389/fgene.2021.617350
Zhu HY, Gao YJ, Wang Y, Liang C, Zhang ZX, Chen Y (2021) LncRNA CRNDE promotes the progression and angiogenesis of pancreatic cancer via miR-451a/CDKN2D axis. Transl Oncol 14:101088. https://doi.org/10.1016/j.tranon.2021.101088
Szafron LM, Balcerak A, Grzybowska EA, Pienkowska-Grela B, Podgorska A, Zub R, Olbryt M, Pamula-Pilat J, Lisowska KM, Grzybowska E, Rubel T, Dansonka-Mieszkowska A, Konopka B, Kulesza M, Lukasik M, Kupryjanczyk J (2015) The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients. Oncotarget 6:43897–43910. https://doi.org/10.18632/oncotarget.6016
Niu YC, Tong J, Shi XF, Zhang T (2020) MicroRNA-654-3p enhances cisplatin sensitivity by targeting QPRT and inhibiting the PI3K/AKT signaling pathway in ovarian cancer cells. Exp Ther Med 20:1467–1479. https://doi.org/10.3892/etm.2020.8878
Zhang Y, Qin X, Jiang J, Zhao W (2020) MicroRNA-126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial-to-mesenchymal transition and ERK/MAPK signaling pathway. Oncol Lett 20:1327–1335. https://doi.org/10.3892/ol.2020.11687
Romani C, Salviato E, Paderno A, Zanotti L, Ravaggi A, Deganello A, Berretti G, Gualtieri T, Marchini S, D’Incalci M, Mattavelli D, Piazza C, Bossi P, Romualdi C, Nicolai P, Bignotti E (2021) Genome-wide study of salivary miRNAs identifies miR-423-5p as promising diagnostic and prognostic biomarker in oral squamous cell carcinoma. Theranostics 11:2987–2999. https://doi.org/10.7150/thno.45157
Liu D, Li B, Shi X, Zhang J, Chen AM, Xu J, Wang W, Huang K, Gao J, Zheng Z, Liu D, Wang H, Shi W, Chen L, Xu J (2021) Cross-platform genomic identification and clinical validation of breast cancer diagnostic biomarkers. Aging (Albany NY) 13:4258–4273. https://doi.org/10.18632/aging.202388
Tang X, Zeng X, Huang Y, Chen S, Lin F, Yang G, Yang N (2018) miR-423-5p serves as a diagnostic indicator and inhibits the proliferation and invasion of ovarian cancer. Exp Ther Med 15:4723–4730. https://doi.org/10.3892/etm.2018.6015
Wei D, Sun L, Feng W (2021) hsa_circ_0058357 acts as a ceRNA to promote nonsmall cell lung cancer progression via the hsamiR243p/AVL9 axis. Mol Med Rep 23(6):470. https://doi.org/10.3892/mmr.2021.12109
Li J, Han X, Gu Y, Wu J, Song J, Shi Z, Chang H, Liu M, Zhang Y (2021) LncRNA MTX2-6 suppresses cell proliferation by acting as ceRNA of miR-574-5p to accumulate SMAD4 in esophageal squamous cell carcinoma. Front Cell Dev Biol 9:654746. https://doi.org/10.3389/fcell.2021.654746
Zhu J, Li X, Zhang S, Liu J, Yao X, Zhao Q, Kou B, Han P, Wang X, Bai Y, Zheng Z, Xu C (2021) Taraxasterol inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in papillary thyroid cancer cells through regulating the Wnt/beta-catenin signaling. Hum Exp Toxicol 40:S87–S95. https://doi.org/10.1177/09603271211023792
Kureishy N, Sapountzi V, Prag S, Anilkumar N, Adams JC (2002) Fascins, and their roles in cell structure and function. BioEssays 24:350–361. https://doi.org/10.1002/bies.10070
Luo A, Yin Y, Li X, Xu H, Mei Q, Feng D (2015) The clinical significance of FSCN1 in non-small cell lung cancer. Biomed Pharmacother 73:75–79. https://doi.org/10.1016/j.biopha.2015.05.014
Wang CQ, Tang CH, Wang Y, Jin L, Wang Q, Li X, Hu GN, Huang BF, Zhao YM, Su CM (2017) FSCN1 gene polymorphisms: biomarkers for the development and progression of breast cancer. Sci Rep 7:15887. https://doi.org/10.1038/s41598-017-16196-6
Cao D, Maitra A, Saavedra JA, Klimstra DS, Adsay NV, Hruban RH (2005) Expression of novel markers of pancreatic ductal adenocarcinoma in pancreatic nonductal neoplasms: additional evidence of different genetic pathways. Mod Pathol 18:752–761. https://doi.org/10.1038/modpathol.3800363
Hu W, Deavers M, Kavanagh JJ, Kudelka AP, Verschraegen CF (2000) Increased expression of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors. Clin Exp Metastasis 18:83–88
Li H, Li Q, Li Y, Sang X, Yuan H, Zheng B (2020) Stannic oxide nanoparticle regulates proliferation, invasion, apoptosis, and oxidative stress of oral cancer cells. Front Bioeng Biotechnol 8:768. https://doi.org/10.3389/fbioe.2020.00768
Cai M, Shao W, Yu H, Hong Y, Shi L (2020) Paeonol inhibits cell proliferation, migration and invasion and induces apoptosis in hepatocellular carcinoma by regulating miR-21-5p/KLF6 axis. Cancer Manag Res 12:5931–5943. https://doi.org/10.2147/CMAR.S254485
Guo L, Kang JS, Kang NJ, Choi YW (2020) S-petasin induces apoptosis and inhibits cell migration through activation of p53 pathway signaling in melanoma B16F10cells and A375cells. Arch Biochem Biophys 692:108519. https://doi.org/10.1016/j.abb.2020.108519
Li F, Huang C, Li Q, Wu X (2018) Construction and comprehensive analysis for dysregulated long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in gastric cancer. Med Sci Monit 24:37–49. https://doi.org/10.12659/msm.905410
Chen Y, Tian T, Li ZY, Wang CY, Deng R, Deng WY, Yang AK, Chen YF, Li H (2019) FSCN1 is an effective marker of poor prognosis and a potential therapeutic target in human tongue squamous cell carcinoma. Cell Death Dis 10:356. https://doi.org/10.1038/s41419-019-1574-5
Du W, Feng Z, Sun Q (2018) LncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathway. Biochem Biophys Res Commun 507:198–202. https://doi.org/10.1016/j.bbrc.2018.11.006
Cao Z, Chen H, Mei X, Li X (2021) Silencing of NACC1 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating the AKT/mTOR signaling pathway. Oncol Lett 22:828. https://doi.org/10.3892/ol.2021.13088
He W, Zhu X, Tang X, Xiang X, Yu J, Sun H (2022) Circ_0027089 regulates NACC1 by targeting miR-136-5p to aggravate the development of hepatitis B virus-related hepatocellular carcinoma. Anticancer Drugs 33:e336–e348. https://doi.org/10.1097/CAD.0000000000001211
Huang FK, Han S, Xing B, Huang J, Liu B, Bordeleau F, Reinhart-King CA, Zhang JJ, Huang XY (2015) Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization. Nat Commun 6:7465. https://doi.org/10.1038/ncomms8465
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QW: concepts, design, writing- original draft preparation; LXW: experimental studies; CYZ: writing- original draft preparation; NB: data acquisition, data analysis; CF: experimental studies; ZMZ: experimental studies; LW: data acquisition, data analysis; ZZG: supervision, writing- reviewing and Editing; All the authors approved for the final version.
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Qiong Wang and Ling-Xiong Wang are first co-authors.
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Wang, Q., Wang, LX., Zhang, CY. et al. LncRNA CRNDE promotes cell proliferation, migration and invasion of ovarian cancer via miR-423-5p/FSCN1 axis. Mol Cell Biochem 477, 1477–1488 (2022). https://doi.org/10.1007/s11010-022-04382-8
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DOI: https://doi.org/10.1007/s11010-022-04382-8