Construction of ceRNA networks reveals differences between distal and proximal colon cancers

Qian,Wenwei; Feng,Yifei; Li,Jie; Peng,Wen; Gu,Qiou; Zhang,Zhiyuan; Ji,Dongjian; Wang,Qingyuan; Zhang,Dongsheng; Sun,Yueming

doi:10.3892/or.2019.7083

Construction of ceRNA networks reveals differences between distal and proximal colon cancers

Authors:
- Wenwei Qian
- Yifei Feng
- Jie Li
- Wen Peng
- Qiou Gu
- Zhiyuan Zhang
- Dongjian Ji
- Qingyuan Wang
- Dongsheng Zhang
- Yueming Sun
View Affiliations

Affiliations: The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: March 21, 2019 https://doi.org/10.3892/or.2019.7083
Pages: 3027-3040

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although colon cancer is often referred to as a homogeneous entity, an increasing number of studies have revealed that colon cancer can be divided according to the anatomic site of the cancer. However, few studies have reported the difference between distal and proximal colon cancer with regard to molecular mechanism, and especially non‑coding RNA molecules. In the present study, the data of 186 colon tumour tissues and 17 adjacent non‑tumour colon tissues in the left colon and 229 colon tumour tissues and 21 adjacent non‑tumour colon tissues in the right colon were obtained from The Cancer Genome Atlas (TCGA). A total of 879 lncRNAs, 165 miRNAs and 2,028 mRNAs were identified as left‑specific RNAs [log2(fold change)>2, FDR<0.01]. There were 916 lncRNAs, 227 miRNAs and 2,069 mRNAs identified in right colon cancer. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways were analysed for 2,028 mRNAs from left colon cancer and 2,069 mRNAs from right colon cancer. After removing the elements of the intersection from side‑specific lncRNAs of the left and right, we identified specific lncRNAs included exclusively in left or right colon cancer, including 277 lncRNAs in left colon cancer and 314 lncRNAs in right colon cancer. Among these lncRNAs, 20 lncRNAs from the left and 25 lncRNAs from the right were revealed to be associated with overall survival. Then, ceRNA networks were constructed. There were 18 lncRNAs, 22 miRNAs and 57 mRNAs included in the left colon cancer ceRNA network and 21 lncRNAs, 27 miRNAs and 55 mRNAs included in the right ceRNA network. In total, 15 lncRNAs were revealed to be significantly related to clinical features, two of which were ascertained by testing the mRNA expression of tissues. In conclusion, our research aimed to detect the difference between colon cancer in the left and the right colon and to assist in the identification of new potential biomarkers to be used for diagnostic and prognostic purposes.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Bufill JA: Colorectal cancer: Evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 113:779–788. 1990. View Article : Google Scholar : PubMed/NCBI
3	Gervaz P, Bucher P and Morel P: Two colons-two cancers: Paradigm shift and clinical implications. J Surg Oncol. 88:261–266. 2004. View Article : Google Scholar : PubMed/NCBI
4	Distler P and Holt PR: Are right- and left-sided colon neoplasms distinct tumors? Dig Dis. 15:302–311. 1997. View Article : Google Scholar : PubMed/NCBI
5	Glebov OK, Rodriguez LM, Nakahara K, Jenkins J, Cliatt J, Humbyrd CJ, DeNobile J, Soballe P, Simon R, Wright G, et al: Distinguishing right from left colon by the pattern of gene expression. Cancer Epidemiol Biomarkers Prev. 12:755–762. 2003.PubMed/NCBI
6	Iacopetta B: Are there two sides to colorectal cancer? Int J Cancer. 101:403–408. 2002. View Article : Google Scholar : PubMed/NCBI
7	Sana J, Faltejskova P, Svoboda M and Slaby O: Novel classes of non-coding RNAs and cancer. J Transl Med. 10:1032012. View Article : Google Scholar : PubMed/NCBI
8	Pan W, Liu L, Wei J, Ge Y, Zhang J, Chen H, Zhou L, Yuan Q, Zhou C and Yang M: A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol Carcinog. 55:90–96. 2016. View Article : Google Scholar : PubMed/NCBI
9	Huang C, Cao L, Qiu L, Dai X, Ma L, Zhou Y, Li H, Gao M, Li W, Zhang Q, et al: Upregulation of H19 promotes invasion and induces epithelial-to-mesenchymal transition in esophageal cancer. Oncol Lett. 10:291–296. 2015. View Article : Google Scholar : PubMed/NCBI
10	Zheng HT, Shi DB, Wang YW, Li XX, Xu Y, Tripathi P, Gu WL, Cai GX and Cai SJ: High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int J Clin Exp Pathol. 7:3174–3181. 2014.PubMed/NCBI
11	Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
12	Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, Popovici V, Vecchione L, Gerster S, Yan P, et al: Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 25:1995–2001. 2014. View Article : Google Scholar : PubMed/NCBI
13	Snaebjornsson P, Jonasson L, Jonsson T, Moller PH, Theodors A and Jonasson JG: Colon cancer in Iceland-a nationwide comparative study on various pathology parameters with respect to right and left tumor location and patients age. Int J Cancer. 127:2645–2653. 2010. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Budinska E, Popovici V, Tejpar S, D'Ario G, Lapique N, Sikora KO, Di Narzo AF, Yan P, Hodgson JG, Weinrich S, et al: Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J Pathol. 231:63–76. 2013. View Article : Google Scholar : PubMed/NCBI
16	Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LC, Lannon WA, Grotzinger C, Del Rio M, et al: A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med. 19:619–625. 2013. View Article : Google Scholar : PubMed/NCBI
17	Zhang DY, Zou XJ, Cao CH, Zhang T, Lei L, Qi XL, Liu L and Wu DH: Identification and functional characterization of long non-coding RNA MIR22HG as a tumor suppressor for hepatocellular carcinoma. Theranostics. 8:3751–3765. 2018. View Article : Google Scholar : PubMed/NCBI
18	Cui Z, An X, Li J, Liu Q and Liu W: LncRNA MIR22HG negatively regulates miR-141-3p to enhance DAPK1 expression and inhibits endometrial carcinoma cells proliferation. Biomed Pharmacother. 104:223–228. 2018. View Article : Google Scholar : PubMed/NCBI
19	Li D, Yang M, Liao A, Zeng B, Liu D, Yao Y, Hu G, Chen X, Feng Z, Du Y, et al: Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer. J Cell Mol Med. 15:136612018.
20	Lu PW, Li L, Wang F and Gu YT: Effects of long non-coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let-7b in breast cancer. J Cell Biochem. 119:4570–4580. 2018. View Article : Google Scholar : PubMed/NCBI
21	Macleod RJ: CaSR function in the intestine: Hormone secretion, electrolyte absorption and secretion, paracrine non-canonical Wnt signaling and colonic crypt cell proliferation. Best Pract Res Clin Endocrinol Metab. 27:385–402. 2013. View Article : Google Scholar : PubMed/NCBI
22	Basu S, Haase G and Ben-Ze'ev A: Wnt signaling in cancer stem cells and colon cancer metastasis. F1000Res. 5:F10002016. View Article : Google Scholar
23	Zarkou V, Galaras A, Giakountis A and Hatzis P: Crosstalk mechanisms between the WNT signaling pathway and long non-coding RNAs. Noncoding RNA Res. 3:42–53. 2018. View Article : Google Scholar : PubMed/NCBI
24	Lecarpentier Y, Claes V, Vallee A and Hébert JL: Interactions between PPAR gamma and the canonical wnt/beta-catenin pathway in type 2 diabetes and colon cancer. PPAR Res. 2017:58790902017. View Article : Google Scholar : PubMed/NCBI
25	Feng W, Wang C, Liang C, Yang H, Chen D, Yu X, Zhao W, Geng D, Li S, Chen Z and Sun M: The dysregulated expression of KCNQ1OT1 and its interaction with downstream factors miR-145/CCNE2 in breast cancer cells. Cell Physiol Biochem. 49:432–446. 2018. View Article : Google Scholar : PubMed/NCBI
26	Gao X, Ge J, Li W, Zhou W and Xu L: LncRNA KCNQ1OT1 ameliorates particle-induced osteolysis through inducing macrophage polarization by inhibiting miR-21a-5p. Biol Chem. 399:375–386. 2018. View Article : Google Scholar : PubMed/NCBI
27	Di Agostino S, Valenti F, Sacconi A, Fontemaggi G, Pallocca M, Pulito C, Ganci F, Muti P, Strano S and Blandino G: Long non-coding MIR205HG depletes Hsa-miR-590-3p leading to unrestrained proliferation in head and neck squamous cell carcinoma. Theranostics. 8:1850–1868. 2018. View Article : Google Scholar : PubMed/NCBI
28	Ma Y, Bu D, Long J, Chai W and Dong J: LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance tamoxifen resistance in breast cancer. J Cell Physiol. 234:2880–2894. 2019. View Article : Google Scholar : PubMed/NCBI
29	Wang L, Liu D, Wu X, Zeng Y, Li L, Hou Y, Li W and Liu Z: Long non-coding RNA (LncRNA) RMST in triple-negative breast cancer (TNBC): Expression analysis and biological roles research. J Cell Physiol. 233:6603–6612. 2018. View Article : Google Scholar : PubMed/NCBI
30	Zhang X, Wang M, Sun H, Zhu T and Wang X: Downregulation of LINC00894-002 contributes to tamoxifen resistance by enhancing the TGF-β signaling pathway. Biochemistry. 83:603–611. 2018.PubMed/NCBI
31	Shen C, Kong B, Liu Y, Xiong L, Shuai W, Wang G, Quan D and Huang H: YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis. Biochem Biophys Res Commun. 505:134–140. 2018. View Article : Google Scholar : PubMed/NCBI
32	Zhang S, Ma H, Zhang D, Xie S, Wang W, Li Q, Lin Z and Wang Y: LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling. Cell Death Dis. 9:7422018. View Article : Google Scholar : PubMed/NCBI
33	Fan S, Fan C, Liu N, Huang K, Fang X and Wang K: Downregulation of the long non-coding RNA ZFAS1 is associated with cell proliferation, migration and invasion in breast cancer. Mol Med Rep. 17:6405–6412. 2018.PubMed/NCBI
34	Li J, Wang W, Xia P, Wan L, Zhang L, Yu L, Wang L, Chen X, Xiao Y and Xu C: Identification of a five-lncRNA signature for predicting the risk of tumor recurrence in patients with breast cancer. Int J Cancer. 143:2150–2160. 2018. View Article : Google Scholar : PubMed/NCBI