Identification of KEY lncRNAs and mRNAs Associated with Oral Squamous Cell Carcinoma Progression

Page: [207 - 215] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Oral squamous cell carcinoma (OSCC) has been the sixth most common cancer worldwide. Emerging studies showed long non-coding RNAs to play a key role in human cancers. However, the molecular mechanisms underlying the initiation and progression of OSCC remained to be further explored.

Objective: The present study aimed to identify differentially expressed lncRNAs and mRNAs in OSCC.

Methods: GSE30784 was analyzed to identify differentially expressed lncRNAs and mRNAs in OSCC. Protein-protein interaction network and co-expression network analyses were performed to reveal the potential roles of OSCC related mRNAs and lncRNAs.

Results: In the present study, we identified 21 up-regulated lncRNAs and 54 down-regulated lncRNAs in OSCC progression. Next, we constructed a lncRNA related co-expression network in OSCC, which included 692 mRNAs and 2193 edges. Bioinformatics analysis showed that lncRNAs were widely co-expressed with regulating type I interferon signaling pathway, extracellular matrix organization, collagen catabolic process, immune response, ECM-receptor interaction, Focal adhesion, and PI3K-Akt signaling pathway. A key network, including lncRNA C5orf66-AS1, C21orf15, LOC100506098, PCBP1-AS1, LOC284825, OR7E14P, HCG22, and FLG-AS1, was found to be involved in the regulation of immune response to tumor cell, Golgi calcium ion transport, negative regulation of vitamin D receptor signaling pathway, and glycerol- 3-phosphate catabolic process. Moreover, we found higher expressions of CYP4F29P, PCBP1- AS1, HCG22, and C5orf66-AS1, which were associated with shorter overall survival time in OSCC samples.

Conclusions: Our analysis can provide novel insights to explore the potential mechanisms underlying OSCC progression.

Keywords: Long non-coding RNAs, oral squamous cell carcinoma, protein-protein interaction analysis, co-expression analysis, biomarker, mRNAs.

Graphical Abstract

[1]
Cancer Genome Atlas N. Cancer Genome Atlas Network Comprehensive genomic characterization of head and neck squamous cell carcinomas Nature 2015; 517(7536): 576-82.
[http://dx.doi.org/10.1038/nature14129] [PMID: 25631445]
[2]
Onken MD, Winkler AE, Kanchi KL, et al. A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease. Clin Cancer Res 2014; 20(11): 2873-84.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0205] [PMID: 24668645]
[3]
Sunkel B, Wu D, Chen Z, et al. Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence. Nucleic Acids Res 2016; 44(9): 4105-22.
[http://dx.doi.org/10.1093/nar/gkv1528] [PMID: 26743006]
[4]
Hosono Y, Niknafs YS, Prensner JR, et al. Oncogenic role of thor, a conserved cancer/testis long non-coding RNA. Cell 2017; 171(7): 1559-1572 e1520..
[http://dx.doi.org/10.1016/j.cell.2017.11.040]
[5]
Zamore PD, Haley B. Ribo-gnome: the big world of small RNAs. Science 2005; 309(5740): 1519-24.
[http://dx.doi.org/10.1126/science.1111444] [PMID: 16141061]
[6]
Kornienko AE, Guenzl PM, Barlow DP, Pauler FM. Gene regulation by the act of long non-coding RNA transcription. BMC Biol 2013; 11: 59.
[http://dx.doi.org/10.1186/1741-7007-11-59] [PMID: 23721193]
[7]
Booy EP, McRae EK, Koul A, Lin F, McKenna SA. The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation. Mol Cancer 2017; 16(1): 109.
[http://dx.doi.org/10.1186/s12943-017-0679-7] [PMID: 28651607]
[8]
Yang F, Bi J, Xue X, et al. Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J 2012; 279(17): 3159-65.
[http://dx.doi.org/10.1111/j.1742-4658.2012.08694.x] [PMID: 22776265]
[9]
Vafadar A, Shabaninejad Z, Movahedpour A, et al. Long non-coding RNAs as epigenetic regulators in cancer. Curr Pharm Des 2019; 25(33): 3563-77.
[http://dx.doi.org/10.2174/1381612825666190830161528] [PMID: 31470781]
[10]
Wang T, Qu X, Jiang J, et al. Diagnostic significance of urinary long non-coding PCA3 RNA in prostate cancer. Oncotarget 2017; 8(35): 58577-86.
[http://dx.doi.org/10.18632/oncotarget.17272] [PMID: 28938580]
[11]
Yan G, Wang X, Yang M, Lu L, Zhou Q. Long non-coding RNA TUG1 promotes progression of oral squamous cell carcinoma through upregulating FMNL2 by sponging miR-219. Am J Cancer Res 2017; 7(9): 1899-912.
[PMID: 28979812]
[12]
Chang SM, Hu WW. Long non-coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA-125b/STAT3 axis. J Cell Physiol 2018; 233(4): 3384-96.
[http://dx.doi.org/10.1002/jcp.26185] [PMID: 28926115]
[13]
Arunkumar G, Murugan AK, Rao HPS, Subbiah S, Rajaraman R, Munirajan AK. Long non-coding RNA CCAT1 is overexpressed in oral squamous cell carcinomas and predicts poor prognosis. Biomed Rep 2017; 6(4): 455-62.
[http://dx.doi.org/10.3892/br.2017.876] [PMID: 28413645]
[14]
Wang X, Liu W, Wang P, Li S. RNA interference of long noncoding RNA HOTAIR suppresses autophagy and promotes apoptosis and sensitivity to cisplatin in oral squamous cell carcinoma. J Oral Pathol Med 2018; 47(10): 930-7.
[http://dx.doi.org/10.1111/jop.12769] [PMID: 30053324]
[15]
Li S, Zhao H, Li J, Zhang A, Wang H. Downregulation of long non-coding RNA LET predicts poor prognosis and increases Notch signaling in non-small cell lung cancer. Oncotarget 2017; 9(1): 1156-68.
[http://dx.doi.org/10.18632/oncotarget.23452] [PMID: 29416684]
[16]
Chen C, Méndez E, Houck J, et al. Gene expression profiling identifies genes predictive of oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2008; 17(8): 2152-62.
[http://dx.doi.org/10.1158/1055-9965.EPI-07-2893] [PMID: 18669583]
[17]
Smyth GK. Limma: linear models for microarray data.In: Gentleman R, Carey V.J., Huber W., Irizarry R.A., Dudoit S. (eds) bioinformatics and computational biology solutions using r and bioconductor. statistics for biology and health. Springer, New York, NY USA. 2005; pp. 397-420..
[18]
Page RD. Treeview. Glasgow, UK: Glasgow University 2001.
[19]
Zhang X, Sun S, Pu JKS, et al. Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis 2012; 48(1): 1-8.
[http://dx.doi.org/10.1016/j.nbd.2012.06.004] [PMID: 22709987]
[20]
Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37(1): 1-13.
[http://dx.doi.org/10.1093/nar/gkn923] [PMID: 19033363]
[21]
Szklarczyk D, Franceschini A, Kuhn M, et al. The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011; 39(Database issue): D561-8.
[http://dx.doi.org/10.1093/nar/gkq973] [PMID: 21045058]
[22]
Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 2003; 4: 2.
[http://dx.doi.org/10.1186/1471-2105-4-2] [PMID: 12525261]
[23]
Zhang Y, Kong Z, Zhang Y, et al. Increased expression of long non-coding RNA GLIDR in prostate cancer. Cancer Biomark 2017; 19(2): 145-50.
[http://dx.doi.org/10.3233/CBM-160166] [PMID: 28211799]
[24]
Dan J, Wang J, Wang Y, et al. LncRNA-MEG3 inhibits proliferation and metastasis by regulating miRNA-21 in gastric cancer. Biomed Pharmacother 2018; 99: 931-8.
[http://dx.doi.org/10.1016/j.biopha.2018.01.164] [PMID: 29710493]
[25]
Yan Q, Tian Y, Hao F. Downregulation of lncRNA UCA1 inhibits proliferation and invasion of cervical cancer cells through miR-206 expression. Oncol Res 2018.
[http://dx.doi.org/10.3727/096504018X15185714083446] [PMID: 29523226]
[26]
Luo J, Chen J, Li H, et al. LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR-143/HMGB1 pathway. Oncol Lett 2017; 14(5): 5556-62.
[http://dx.doi.org/10.3892/ol.2017.6886] [PMID: 29113184]
[27]
Koch L. Functional genomics: Screening for lncRNA function. Nat Rev Genet 2017; 18(2): 70.
[PMID: 28045101]
[28]
Hu J, Qian Y, Peng L, et al. Long noncoding RNA EGFR-AS1 promotes cell proliferation by increasing egfr mrna stability in gastric cancer. Cell Physiol Biochem 2018; 49(1): 322-34.
[http://dx.doi.org/10.1159/000492883] [PMID: 30138934]
[29]
Chen P, Wang R, Yue Q, Hao M. Long non-coding RNA TTN-AS1 promotes cell growth and metastasis in cervical cancer via miR-573/E2F3. Biochem Biophys Res Commun 2018; 503(4): 2956-62.
[http://dx.doi.org/10.1016/j.bbrc.2018.08.077] [PMID: 30135013]
[30]
Jiang L, Yu X, Ma X, et al. Identification of transcription factor-miRNA-lncRNA feed-forward loops in breast cancer subtypes. Comput Biol Chem 2019; 78: 1-7.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.11.008] [PMID: 30476706]
[31]
Hu X, Qiu Z, Zeng J, Xiao T, Ke Z, Lyu H. A novel long non-coding RNA, AC012456.4, as a valuable and independent prognostic biomarker of survival in oral squamous cell carcinoma. PeerJ 2018; 6e5307
[http://dx.doi.org/10.7717/peerj.5307] [PMID: 30128179]
[32]
Chou KC. Structural bioinformatics and its impact to biomedical science. Curr Med Chem 2004; 11(16): 2105-34.
[http://dx.doi.org/10.2174/0929867043364667] [PMID: 15279552]
[33]
Liu B, Liu F, Wang X, Chen J, Fang L, Chou KC. Pse-in-One: a web server for generating various modes of pseudo components of DNA, RNA, and protein sequences. Nucleic Acids Res 2015; 43(W1)W65-71
[http://dx.doi.org/10.1093/nar/gkv458] [PMID: 25958395]
[34]
Du P, Wang X, Xu C, Gao Y. PseAAC-Builder: a cross-platform stand-alone program for generating various special Chou’s pseudo-amino acid compositions. Anal Biochem 2012; 425(2): 117-9.
[http://dx.doi.org/10.1016/j.ab.2012.03.015] [PMID: 22459120]
[35]
Shabaninejad Z, Vafadar A, Movahedpour A, et al. Circular RNAs in cancer: new insights into functions and implications in ovarian cancer. J Ovarian Res 2019; 12(1): 84.
[http://dx.doi.org/10.1186/s13048-019-0558-5] [PMID: 31481095]
[36]
Wang W, Gao F, Zhao Z, et al. Integrated analysis of lncrna-mrna co-expression profiles in patients with moyamoya disease. Sci Rep 2017; 7: 42421.
[http://dx.doi.org/10.1038/srep42421] [PMID: 28176861]
[37]
Naeli P, Pourhanifeh MH, Karimzadeh MR, et al. Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role. Crit Rev Oncol Hematol 2020; •••145102854
[http://dx.doi.org/10.1016/j.critrevonc.2019.102854] [PMID: 31877535]
[38]
Xiao Q, Luo J, Liang C, et al. Identifying lncrna and mrna co-expression modules from matched expression data in ovarian cancer . IEEE/ACM Trans Comput Biol Bioinform 2020;17(2): 623-34..
[39]
Saeedi Borujeni MJ, Esfandiary E, Baradaran A, et al. Molecular aspects of pancreatic β-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA. J Cell Physiol 2019; 234(6): 8411-25.
[http://dx.doi.org/10.1002/jcp.27755] [PMID: 30565679]
[40]
Zhang PB, Cui J. Letter to the editor regarding the article “long non-coding rna spry4-it1 can predict poor prognosis in digestive system malignancies: a meta-analysis”. Pathol Oncol Res 2020; 26(1): 589-90.
[PMID: 30091006]
[41]
Li H, Gong M, Zhao M, Wang X, Cheng W, Xia Y. LncRNAs KB- 1836B5, LINC00566 and FAM27L are associated with the survival time of patients with ovarian cancer. Oncol Lett 2018; 16(3): 3735- 45..
[http://dx.doi.org/10.3892/ol.2018.9143] [PMID: 30127984]
[42]
Wang D, Li J, Cai F, et al. Overexpression of Mapt-As1 is associated with better patient survival in breast cancer. Biochem Cell Biol 2019; 97(2): 158-64.
[PMID: 30074401]