Skip to main content

Advertisement

SpringerLink
Log in

Potential role of lnc-METRNL-1 in the occurrence and prognosis of oral squamous cell carcinoma

  • Original Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck with poor prognosis. This study aimed to explore the role of lnc-METRNL-1 in occurrence and prognosis of OSCC patients. Expression of lnc-METRNL-1 was compared between OSCC samples and paracancerous samples from The Cancer Genome Atlas (TCGA) database. Additionally, the lnc-METRNL-1 expression in cell lines was detected by using qRT-PCR. The overall survival (OS) was estimated based on the Kaplan–Meier and the immune cell infiltration was evaluated using CIBERSORT. Significantly enriched biological pathways were identified by Gene-set enrichment analysis (GSEA). Differential expression analysis was done in edgeR package. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of differential expression genes were conducted using DAVID version 6.8. The lnc-METRNL-1 expression in OSCC was significantly lower than that in paracancerous samples, and patients with low lnc-METRNL-1 expression had poorer OS. Additionally, lnc-METRNL-1 was significantly down-regulated in OSCC cell lines compared with normal cell line. High expression of lnc-METRNL-1 was closely associated with the activation of several tumor metabolic and metabolism-related pathways. Besides, aberrant lnc-METRNL-1 expression was found to be related to the differential infiltration of immune cells in tumor tissue, such as regulatory T cells, and Macrophages. Low lnc-METRNL-1 expression was probably a poor prognostic biomarker for OSCC patients. Moreover, the potential role of lnc-METRNL-1 in the onset of OSCC was partly revealed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The data that support the findings of this study are available in TCGA at (https://tcga-data.nci.nih.gov/tcga/).

References

  • Akhade VS, Dighe SN, Kataruka S, Rao MR (2016) Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells. Nucleic Acids Res 44(1):387–401

    Article  CAS  PubMed  Google Scholar 

  • Alhamarneh O, Amarnath SM, Stafford ND, Greenman J (2008) Regulatory T cells: what role do they play in antitumor immunity in patients with head and neck cancer? Head Neck 30(2):251–261

    Article  PubMed  Google Scholar 

  • Anderson KM, Wygodny JB, Ondrey F, Harris J (1988) Human PC-3 prostate cell line DNA synthesis is suppressed by eicosatetraynoic acid, an in vitro inhibitor of arachidonic acid metabolism. Prostate 12(1):3–12

    Article  CAS  PubMed  Google Scholar 

  • Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A, Sica A (2006) A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107(5):2112–2122

    Article  CAS  PubMed  Google Scholar 

  • Brash AR (1999) Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem 274(34):23679–23682

    Article  CAS  PubMed  Google Scholar 

  • Chen F, Li Y, Feng Y, He X, Wang L (2016) Evaluation of antimetastatic effect of lncRNA-ATB siRNA delivered using ultrasound-targeted microbubble destruction. DNA Cell Biol 35(8):393–397

    Article  PubMed  Google Scholar 

  • Chen Y, Mao ZD, Shi YJ, Qian Y, Liu ZG, Yin XW, Zhang Q (2019) Comprehensive analysis of miRNA-mRNA-lncRNA networks in severe asthma. Epigenomics 11(2):115–131

    Article  CAS  PubMed  Google Scholar 

  • Dan H, Liu S, Liu J, Liu D, Yin F, Wei Z, Wang J, Zhou Y, Jiang L, Ji N, Zeng X, Li J, Chen Q (2020) RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-kappaB pathway in oral squamous cell carcinoma. Mol Oncol 14(4):795–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Camargo Cancela M, Voti L, Guerra-Yi M, Chapuis F, Mazuir M, Curado MP (2010) Oral cavity cancer in developed and in developing countries: population-based incidence. Head Neck 32(3):357–367

    PubMed  Google Scholar 

  • Deng J, Wu M (2023) COX10-AS1-mediated miR-361-5p regulated cell invasion and migration by targeting SPRY1 in oral squamous cell carcinoma. Am J Transl Res 15(3):2191–2206

    PubMed  PubMed Central  Google Scholar 

  • Du J, Su W, Li X, Zu T, Bai J, Zhang W, Zhou W (2023) LINC00525 promotes tumour growth and epithelial-mesenchymal transition as an oncogene in oral squamous cell carcinoma. Oral Dis. https://doi.org/10.1111/odi.14613

    Article  PubMed  Google Scholar 

  • Elahi A, Bendaly J, Zheng Z, Muscat JE, Richie JP Jr, Schantz SP, Lazarus P (2003) Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk. Cancer 98(4):872–880

    Article  CAS  PubMed  Google Scholar 

  • Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S (2013) Tumor associated macrophages and neutrophils in cancer. Immunobiology 218(11):1402–1410

    Article  CAS  PubMed  Google Scholar 

  • Gao P, Wei GH (2017) Genomic insight into the role of lncRNA in cancer susceptibility. Int J Mol Sci 18(6):1239

    Article  PubMed  PubMed Central  Google Scholar 

  • Guengerich FP (1999) Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol 39:1–17

    Article  CAS  PubMed  Google Scholar 

  • Gueraud F, Paris A (1998) Glucuronidation: a dual control. Gen Pharmacol 31(5):683–688

    Article  CAS  PubMed  Google Scholar 

  • Hadji F, Boulanger MC, Guay SP, Gaudreault N, Amellah S, Mkannez G, Bouchareb R, Marchand JT, Nsaibia MJ, Guauque-Olarte S, Pibarot P, Bouchard L, Bosse Y, Mathieu P (2016) Altered DNA methylation of long noncoding RNA H19 in calcific aortic valve disease promotes mineralization by silencing NOTCH1. Circulation 134(23):1848–1862

    Article  CAS  PubMed  Google Scholar 

  • Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30(6):445–600

    Article  CAS  PubMed  Google Scholar 

  • Hermans IF, Ritchie DS, Yang J, Roberts JM, Ronchese F (2000) CD8+ T cell-dependent elimination of dendritic cells in vivo limits the induction of antitumor immunity. J Immunol 164(6):3095–3101

    Article  CAS  PubMed  Google Scholar 

  • Imai Y, Kubota Y, Yamamoto S, Tsuji K, Shimatani M, Shibatani N, Takamido S, Matsushita M, Okazaki K (2005) Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study. J Gastroenterol Hepatol 20(2):287–293

    Article  CAS  PubMed  Google Scholar 

  • Jain AK, Xi Y, McCarthy R, Allton K, Akdemir KC, Patel LR, Aronow B, Lin C, Li W, Yang L, Barton MC (2016) LncPRESS1 Is a p53-regulated LncRNA that safeguards pluripotency by disrupting SIRT6-mediated de-acetylation of histone H3K56. Mol Cell 64(5):967–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li B, Lv Y, Zhang C, Xiang C (2023) lncRNA HOXA11-AS maintains the stemness of oral squamous cell carcinoma stem cells and reduces the radiosensitivity by targeting miR-518a-3p/PDK1. J Oral Pathol Med 52(3):216–225

    Article  CAS  PubMed  Google Scholar 

  • Liang S, Zhang S, Wang P, Yang C, Shang C, Yang J, Wang J (2017) LncRNA, TUG1 regulates the oral squamous cell carcinoma progression possibly via interacting with Wnt/beta-catenin signaling. Gene 608:49–57

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Peng WX, Mo YY, Luo D (2017) MALAT1-mediated tumorigenesis. Front Biosci (Landmark Ed) 22:66–80

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Liu Q, Wang X, Liu L, Shi L, Li H (2022) Multiomics immune-related lncRNA analysis of oral squamous cell carcinoma and its correlation with prognosis. Dis Markers 2022:6106503

    Article  PubMed  PubMed Central  Google Scholar 

  • Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA (2015) Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 12(5):453–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panzarella V, Pizzo G, Calvino F, Compilato D, Colella G, Campisi G (2014) Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables. Int J Oral Sci 6(1):39–45

    Article  PubMed  Google Scholar 

  • Peng WX, Koirala P, Mo YY (2017) LncRNA-mediated regulation of cell signaling in cancer. Oncogene 36(41):5661–5667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prizment AE, Vierkant RA, Smyrk TC, Tillmans LS, Nelson HH, Lynch CF, Pengo T, Thibodeau SN, Church TR, Cerhan JR, Anderson KE, Limburg PJ (2017) Cytotoxic T cells and granzyme B associated with improved colorectal cancer survival in a prospective cohort of older women. Cancer Epidemiol Biomarkers Prev 26(4):622–631

    Article  CAS  PubMed  Google Scholar 

  • Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17(1):47–62

    Article  CAS  PubMed  Google Scholar 

  • Radmark O, Samuelsson B (2009) 5-Lipoxygenase: mechanisms of regulation. J Lipid Res 50(Suppl):S40-45

    Article  PubMed  PubMed Central  Google Scholar 

  • Rio DC, Ares M Jr, Hannon GJ, Nilsen TW (2010) Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb Protoc. https://doi.org/10.1093/bioinformatics/btp616

    Article  PubMed  Google Scholar 

  • Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140

    Article  CAS  PubMed  Google Scholar 

  • Rose DP (1997) Dietary fat, fatty acids and breast cancer. Breast Cancer 4(1):7–16

    Article  CAS  PubMed  Google Scholar 

  • Rose DP, Connolly JM (1991) Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines. Prostate 18(3):243–254

    Article  CAS  PubMed  Google Scholar 

  • Scripture CD, Sparreboom A, Figg WD (2005) Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol 6(10):780–789

    Article  CAS  PubMed  Google Scholar 

  • Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao TR, Zheng ZN, Chen YC, Wu QQ, Huang GZ, Li F, Zeng WS, Lv XZ (2019) LncRNA AC007271.3 promotes cell proliferation, invasion, migration and inhibits cell apoptosis of OSCC via the Wnt/beta-catenin signaling pathway.". Life Sci 239:117087

    Article  CAS  PubMed  Google Scholar 

  • Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29

    Article  PubMed  Google Scholar 

  • Sun L, Kang X, Wang C, Wang R, Yang G, Jiang W, Wu Q, Wang Y, Wu Y, Gao J, Chen L, Zhang J, Tian Z, Zhu G, Sun S (2023) Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma. Cell Discov 9(1):28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering CV (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607–D613

    Article  CAS  PubMed  Google Scholar 

  • Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjostedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Ponten F (2015) Proteomics. Tissue-based map of the human proteome. Science 347(6220):1260419

    Article  PubMed  Google Scholar 

  • Wang L, Cho KB, Li Y, Tao G, Xie Z, Guo B (2019) Long noncoding RNA (lncRNA)-mediated competing endogenous rna networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int J Mol Sci 20(22):5758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Welsch CW (1992) Relationship between dietary fat and experimental mammary tumorigenesis: a review and critique. Cancer Res 52(7 Suppl):2040s–2048s

    CAS  PubMed  Google Scholar 

  • Yang C, Zheng X (2022) Identification of a hypoxia-related lncRNA biomarker signature for head and neck squamous cell carcinoma. J Oncol 2022:6775496

    PubMed  PubMed Central  Google Scholar 

  • Yang Y, Chen D, Liu H, Yang K (2019) Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma. Cell Death Dis 10(2):41

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Liu M, Zhang Z, Chen D, Chen G, Liu M (2022) Machine learning based identification of hub genes in renal clear cell carcinoma using multi-omics data. Methods 207:110–117

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Wang F, Yu Y (2023) LncRNA HOXD-AS1 promotes oral squamous cell carcinoma by sponging miR-203a-5p. Oral Dis 29(4):1505–1512

    Article  PubMed  Google Scholar 

  • Zhou RS, Zhang EX, Sun QF, Ye ZJ, Liu JW, Zhou DH, Tang Y (2019) Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue. BMC Cancer 19(1):779

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The datasets of this study are obtained by the Cancer Genome Atlas database. We are grateful to them for establishing the database and making them publicly accessible.

Funding

This study was supported by the grants from Tianjin Stomatology Hospital, School of Medicine, NanKai University. Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction (Grant No. HWZX017).

Author information

Authors and Affiliations

  1. Department of Emergency and General Dentistry, Tianjin Stomatology Hospital, Hospital of Stomatology, NanKai University·Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, No. 75 Dagubei Road, Heping District, Tianjin, 300041, China

    Chenguang Zhao, Yingrui Zhou, Jinhui Wang, Chunlin Liu & Xi Wang

  2. Department of Oral and Maxillofacial Surgery, Tianjin Stomatology Hospital, Hospital of Stomatology, NanKai University·Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, No. 75 Dagubei Road, Heping District, Tianjin, 300041, China

    Zhiling Zhang & Hao Liu

Authors
  1. Chenguang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhiling Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yingrui Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinhui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chunlin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CZ, ZZ and YZ: Conceptualization, Writing-original draft, Formal analysis. Data curation, Project administration, JW, CL and XW: Data curation, Formal analysis, Data interpretation. HL: Writing-review & editing. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Chenguang Zhao or Hao Liu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Research involving human participants and/or animals

All clinical specimens were collected from Tianjin Stomatological Hospital. Our experiments were approved by ethics committee of Tianjin Stomatological Hospital (Ethic Code: 20220217), in line with The Helsinki Declaration.

Informed consent

The informed consents were obtained from all subjects.

Supplementary Information

Below is the link to the electronic supplementary material.

13205_2023_3674_MOESM1_ESM.jpg

Supplementary file1 (JPG 8611 KB) Figure S1. The differentially expressed lncRNAs between OSCC samples and normal samples. (A) The volcano plot of differentially expressed lncRNAs. (B) The heat map of differentially expressed lncRNAs

13205_2023_3674_MOESM2_ESM.jpg

Supplementary file2 (JPG 7421 KB) Figure S2. Kaplan Meier (KM) survival curves of different subgroups. A. KM curve of samples with Age > 61 years. B. KM curve of male patient. C. KM curve of patients at the advanced stage (Stage III+IV). D. KM curve of patients in G1+G2. E. KM curve of patients in G3+G4. F. KM curve of patients with Perineural invasion

13205_2023_3674_MOESM3_ESM.tif

Supplementary file3 (TIF 9253 KB) Figure S3. The expression of lnc-METRNL-1 is correlated with the relative immune infiltration level of OSCC patients. A. Relative proportion of 22 immune cells infiltrated in all patients. B. Correlation matrix of the proportion of 22 types of immune infiltrating cells. Red represents positive correlation and blue represents negative correlation. The darker the color, the greater the correlation. C. Violin diagram of relative infiltration levels of immune cells with significantly different infiltration ratios between the high and low lnc-METRNL-1 expression groups. Different colors represent high and low risk groups, and the vertical axis is the relative infiltration ratio of different immune cells. * Stands for P value < 0.05, ** Stands for P value < 0.01, *** Stands for P value < 0.001, **** Stands for P value < 0.0001. D. The correlation between lnc-METRNL-1 and T cells CD4 Memory recall, T Cells Regulatory (Tregs), Macrophages M1, Neutrophils

Supplementary file4 (XLSX 32 KB)

Supplementary file5 (DOCX 23 KB)

Supplementary file6 (XLSX 12 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, C., Zhang, Z., Zhou, Y. et al. Potential role of lnc-METRNL-1 in the occurrence and prognosis of oral squamous cell carcinoma. 3 Biotech 13, 256 (2023). https://doi.org/10.1007/s13205-023-03674-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-023-03674-0

Keywords

Search

Navigation