Long non‑coding RNA SNHG20 promotes colorectal cancer cell proliferation, migration and invasion via miR‑495/STAT3 axis

Wang,Yu; Fu,Jianying; Yang,Lili; Liang,Zhi

doi:10.3892/mmr.2020.11669

Long non‑coding RNA SNHG20 promotes colorectal cancer cell proliferation, migration and invasion via miR‑495/STAT3 axis

Authors:
- Yu Wang
- Jianying Fu
- Lili Yang
- Zhi Liang
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Affiliations: Department of Gastroenterology Endoscopy, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Anorectal Surgery, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: November 5, 2020 https://doi.org/10.3892/mmr.2020.11669
Article Number: 31
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the primary causes of cancer‑associated mortality worldwide. However, the potential molecular mechanism of CRC progression remains unknown. Long non‑coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to be involved in the development and progression of a variety of tumors, including CRC. However, the involvement of SNHG20 in CRC progression remains unclear. The aim of the present study was to investigate the functional role and molecular mechanism of SNHG20 in CRC progression. In the present study, SNHG20 expression was found to be significantly upregulated in CRC tissues and cell lines. Association analysis indicated that high SNHG20 expression was significantly association with greater tumor size (P=0.014), tumor invasion depth (P=0.019), positive lymph node status (P=0.022), distant metastasis (P=0.017) and advanced tumor node metastasis stage (P=0.038). Loss‑of‑function experiments indicated that SNHG20 knockdown could significantly suppress proliferation, migration and invasion in vitro. Notably, SNHG20 knockdown significantly inhibited tumor growth and lung metastasis in vivo. Bioinformatics analysis and luciferase reporter assays confirmed that microRNA (miR)‑495 was a direct target of SNHG20. Rescue assays indicated that miR‑495 inhibitor reversed the suppressive effects of SNHG20 knockdown on CRC progression. Moreover, STAT3 was identified as a downstream target of miR‑495 in CRC. STAT3 overexpression partially rescued the inhibitory effects of SNHG20 knockdown on CRC progression. Taken together, the results revealed that SNHG20 facilitated CRC progression by regulating STAT3 expression and by sponging miR‑495.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S and Tabernero J: Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 17:79–92. 2017. View Article : Google Scholar : PubMed/NCBI
3	Sridharan M, Hubbard JM and Grothey A: Colorectal cancer: How emerging molecular understanding affects treatment decisions. Oncology (Williston Park). 28:110–118. 2014.PubMed/NCBI
4	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar : PubMed/NCBI
5	Shi X, Sun M, Liu H, Yao Y and Song Y: Long non-coding RNAs: A new frontier in the study of human diseases. Cancer Lett. 339:159–166. 2013. View Article : Google Scholar : PubMed/NCBI
6	Hua F, Liu S, Zhu L, Ma N, Jiang S and Yang J: Highly expressed long non-coding RNA NNT-AS1 promotes cell proliferation and invasion through wnt/β-catenin signaling pathway in cervical cancer. Biomed Pharmacother. 92:1128–1134. 2017. View Article : Google Scholar : PubMed/NCBI
7	Ge X, Li GY, Jiang L, Jia L, Zhang Z, Li X, Wang R, Zhou M, Zhou Y, Zeng Z, et al: Long noncoding RNA CAR10 promotes lung adenocarcinoma metastasis via miR-203/30/SNAI axis. Oncogene. 38:3061–3076. 2019. View Article : Google Scholar : PubMed/NCBI
8	Zhang D, Cao C, Liu L and Wu D: Up-Regulation of lncRNA SNHG20 predicts poor prognosis in hepatocellular carcinoma. J Cancer. 7:608–617. 2016. View Article : Google Scholar : PubMed/NCBI
9	Chen Z, Chen X, Chen P, Yu S, Nie F, Lu B, Zhang T, Zhou Y, Chen Q, Wei C, et al: Long non-coding RNA SNHG20 promotes non-small cell lung cancer cell proliferation and migration by epigenetically silencing of P21 expression. Cell Death Dis. 8:e30922017. View Article : Google Scholar : PubMed/NCBI
10	Wu J, Zhao W, Wang Z, Xiang X, Zhang S and Liu L: Long non-coding RNA SNHG20 promotes the tumorigenesis of oral squamous cell carcinoma via targeting miR-197/LIN28 axis. J Cell Mol Med. 23:680–688. 2019. View Article : Google Scholar : PubMed/NCBI
11	Wu X, Xiao Y, Zhou Y, Zhou Z and Yan W: lncRNA SNHG20 promotes prostate cancer migration and invasion via targeting the miR-6516-5p/SCGB2A1 axis. Am J Transl Res. 11:5162–5169. 2019.PubMed/NCBI
12	Li C, Zhou L, He J, Fang XQ, Zhu SW and Xiong MM: Increased long noncoding RNA SNHG20 predicts poor prognosis in colorectal cancer. BMC Cancer. 16:6552016. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Salmena L, Poliseno L, Tay Y, Kats L and Pandolf PP: A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
15	Yan LK, Yao JF and Qiu J: miRNA-495 suppresses proliferation and migration of colorectal cancer cells by targeting FAM83D. Biomed Pharmacother. 96:974–981. 2017. View Article : Google Scholar : PubMed/NCBI
16	Zhou C, Tong Y, Wawrowsky K and Melmed S: PTTG acts as a STAT3 target gene for colorectal cancer cell growth and motility. Oncogene. 33:851–861. 2014. View Article : Google Scholar : PubMed/NCBI
17	Cai Y, Sheng Z, Chen Y and Wang J: LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating miR-138/sirt6 axis. Aging (Albany NY). 11:3041–3054. 2019. View Article : Google Scholar : PubMed/NCBI
18	Cui N, Liu J, Xia H and Xu D: LncRNA SNHG20 contributes to cell proliferation and invasion by upregulating ZFX expression sponging miR-495-3p in gastric cancer. J Cell Biochem. 120:3114–3123. 2019. View Article : Google Scholar : PubMed/NCBI
19	Wang W, Luo P, Guo W, Shi Y, Xu D, Zheng H and Jia L: LncRNA SNHG20 knockdown suppresses the osteosarcoma tumorigenesis through the mitochondrial apoptosis pathway by miR-139/RUNX2 axis. Biochem Biophys Res Commun. 503:1927–1933. 2018. View Article : Google Scholar : PubMed/NCBI
20	Li X, Xue Y, Liu X, Zheng J, Shen S, Yang C, Chen J, Li Z, Liu L, Ma J, Ma T and Liu Y: ZRANB2/SNHG20/FOXK1 axis regulates vasculogenic mimicry formation in glioma. J Exp Clin Cancer Res. 38:682019. View Article : Google Scholar : PubMed/NCBI
21	Li Z, Cao Y, Jie Z, Liu Y, Li Y, Li Y, Li J, Zhu G, Liu Z, Tu Y, et al: miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3. Cancer Lett. 323:41–47. 2012. View Article : Google Scholar : PubMed/NCBI
22	Li JZ, Wang ZL, Xu WH, Li Q, Gao L and Wang ZM: MicroRNA-495 regulates migration and invasion in prostate cancer cells via targeting akt and mTOR signaling. Cancer Invest. 34:181–188. 2016. View Article : Google Scholar : PubMed/NCBI
23	Chu H, Chen X, Wang H, Du Y, Wang Y, Zang W, Li P, Li J, Chang J, Zhao G and Zhang G: miR-495 regulates proliferation and migration in NSCLC by targeting MTA3. Tumour Biol. 35:3487–3494. 2014. View Article : Google Scholar : PubMed/NCBI
24	Xu YY, Tian J, Hao Q and Yin LR: MicroRNA-495 downregulates FOXC1 expression to suppress cell growth and migration in endometrial cancer. Tumour Biol. 37:239–251. 2016. View Article : Google Scholar : PubMed/NCBI
25	Hwang-Verslues WW, Chang PH, Wei PC, Yang CY, Huang CK, Kuo WH, Shew JY, Chang KJ, Lee EY and Lee WH: miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1. Oncogene. 30:2463–2474. 2011. View Article : Google Scholar : PubMed/NCBI
26	Bai Z, Wang J, Wang T, Li Y, Zhao X, Wu G, Yang Y, Deng W and Zhang Z: The miR-495/Annexin A3/P53 axis inhibits the invasion and EMT of colorectal cancer cells. Cell Physiol Biochem. 44:1882–1895. 2017. View Article : Google Scholar : PubMed/NCBI
27	He Z, Dang J, Song A, Cui X, Ma Z and Zhang Z: NEAT1 promotes colon cancer progression through sponging miR-495-3p and activating CDK6 in vitro and in vivo. J Cell Physiol. 234:19582–19591. 2019. View Article : Google Scholar : PubMed/NCBI
28	Yuan J, Zhang F and Niu R: Multiple regulation pathways and pivotal biological functions of STAT3 in cancer. Sci Rep. 5:176632015. View Article : Google Scholar : PubMed/NCBI
29	Morikawa T, Baba Y, Yamauchi M, Kuchiba A, Nosho K, Shima K, Tanaka N, Huttenhower C, Frank DA, Fuchs CS and Ogino S: STAT3 expression, molecular features, inflammation patterns and prognosis in a database of 724 colorectal cancers. Clin Cancer Res. 17:1452–1462. 2011. View Article : Google Scholar : PubMed/NCBI
30	Zhang P, Zhao Y, Zhu X, Sedwick D, Zhang X and Wang Z: Cross-Talk between phospho-STAT3 and PLCγ1 plays a critical role in colorectal tumorigenesis. Mol Cancer Res. 9:1418–1428. 2011. View Article : Google Scholar : PubMed/NCBI