Long non‑coding RNA SNHG12 promotes proliferation and invasion of colorectal cancer cells by acting as a molecular sponge of microRNA‑16

Liu,Yuehua; Zhou,Jingyu; Wang,Shalong; Song,Yuliang; Zhou,Jianping; Ren,Feng

doi:10.3892/etm.2019.7650

Long non‑coding RNA SNHG12 promotes proliferation and invasion of colorectal cancer cells by acting as a molecular sponge of microRNA‑16

Authors:
- Yuehua Liu
- Jingyu Zhou
- Shalong Wang
- Yuliang Song
- Jianping Zhou
- Feng Ren
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Affiliations: Department of Geriatric Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: June 7, 2019 https://doi.org/10.3892/etm.2019.7650
Pages: 1212-1220
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding (lnc)RNA small nucleolar RNA host gene 12 (SNHG12) has an oncogenic role in various common human cancer types, including colorectal cancer (CRC). However, the detailed regulatory mechanisms of SNHG12 in CRC cells have remained largely elusive, and the investigation thereof was the purpose of the present study. Polymerase chain reaction analysis was performed to examine the expression of lncRNA and microRNA (miR). Cell Counting Kit‑8 and Transwell assays were used to assess cell proliferation and invasion. A luciferase reporter assay was performed to confirm a predicted targeting association between lncRNA and miR. It was observed that SNHG12 was markedly upregulated in CRC tissues when compared with that in adjacent non‑tumour tissues, and its high expression was associated with CRC progression, as well as poor prognosis of patients. In addition, the expression of SNHG12 was higher in CRC cell lines when compared with that in a normal intestinal epithelial cell line. Knockdown of SNHG12 significantly inhibited CRC cell proliferation and invasion, while ectopic overexpression of SNHG12 had the opposite effect. A Bioinformatics analysis predicted that SNHG12 and miR‑16 have complementary binding sites, which was confirmed by a luciferase reporter gene assay. The expression levels of miR‑16 were markedly decreased in CRC tissues and cell lines compared with those in normal tissues or cells, and were inversely correlated with the expression levels of SNHG12 in CRC tissues. Furthermore, silencing of miR‑16 eliminated the suppressive effects of SNHG12 knockdown on CRC cell proliferation and invasion. In conclusion, the present study demonstrated that SNHG12 promotes CRC cell proliferation and invasion, at least in part, by acting as a molecular sponge of miR‑16, suggesting that SNHG12 may be a promising therapeutic target for CRC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	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
3	Li JW, Huang CZ, Li JH, Yuan JH, Chen QH, Zhang WF, Xu ZS, Liu YP, Li Y, Zhan MX and Lu LG: Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer. Oncol Rep. 40:2215–2223. 2018.PubMed/NCBI
4	Cen C, Li J, Liu J, Yang M, Zhang T, Zuo Y, Lin C and Li X: Long noncoding RNA LINC01510 promotes the growth of colorectal cancer cells by modulating MET expression. Cancer Cell Int. 18:452018. View Article : Google Scholar : PubMed/NCBI
5	Price TJ, Tang M, Gibbs P, Haller DG, Peeters M, Arnold D, Segelov E, Roy A, Tebbutt N, Pavlakis N, et al: Targeted therapy for metastatic colorectal cancer. Expert Rev Anticancer Ther. 18:991–1006. 2018. View Article : Google Scholar : PubMed/NCBI
6	Islam F, Gopalan V, Vider J, Wahab R, Ebrahimi F, Lu CT, Kasem K and Lam AKY: MicroRNA-186-5p overexpression modulates colon cancer growth by repressing the expression of the FAM134B tumour inhibitor. Exp Cell Res. 357:260–270. 2017. View Article : Google Scholar : PubMed/NCBI
7	Xiao Z, Qu Z, Chen Z, Fang Z, Zhou K, Huang Z, Guo X and Zhang Y: LncRNA HOTAIR is a prognostic biomarker for the proliferation and chemoresistance of colorectal cancer via MiR-203a-3p-mediated Wnt/β-catenin signaling pathway. Cell Physiol Biochem. 46:1275–1285. 2018. View Article : Google Scholar : PubMed/NCBI
8	Xie B, Deng Z, Pan Y, Fu C, Fan S, Tao Y, Zhou J and Xiao D: Post-transcriptional regulation DPC4 gene by miR-190 in colorectal cancer cells. J Cancer Res Ther. 14:838–843. 2018. View Article : Google Scholar : PubMed/NCBI
9	Liu K, Yao H, Wen Y, Zhao H, Zhou N, Lei S and Xiong L: Functional role of a long non-coding RNA LIFR-AS1/miR-29a/TNFAIP3 axis in colorectal cancer resistance to pohotodynamic therapy. Biochim Biophys Acta. 1864:2871–2880. 2018. View Article : Google Scholar
10	Liao D, Li T, Ye C, Zeng L, Li H, Pu X, Ding C, He Z and Huang GL: miR-221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells. Exp Ther Med. 15:1712–1717. 2018.PubMed/NCBI
11	Yunusov D, Anderson L, DaSilva LF, Wysocka J, Ezashi T, Roberts RM and Verjovski-Almeida S: HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines. Sci Rep. 6:327532016. View Article : Google Scholar : PubMed/NCBI
12	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
13	Zhou Y, Chen Y, Ding W, Hua Z, Wang L, Zhu Y, Qian H and Dai T: LncRNA UCA1 impacts cell proliferation, invasion, and migration of pancreatic cancer through regulating miR-96/FOXO3. IUBMB Life. 70:276–290. 2018. View Article : Google Scholar : PubMed/NCBI
14	Peng Z, Liu C and Wu M: New insights into long noncoding RNAs and their roles in glioma. Mol Cancer. 17:612018. View Article : Google Scholar : PubMed/NCBI
15	Smolle MA and Pichler M: The role of long non-coding RNAs in osteosarcoma. Noncoding RNA. 4:E72018.PubMed/NCBI
16	Xu S, Kong D, Chen Q, Ping Y and Pang D: Oncogenic long noncoding RNA landscape in breast cancer. Mol Cancer. 16:1292017. View Article : Google Scholar : PubMed/NCBI
17	Wang JZ, Xu CL, Wu H and Shen SJ: LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Braz J Med Biol Res. 50:e60792017. View Article : Google Scholar : PubMed/NCBI
18	Lan T, Ma W, Hong Z, Wu L, Chen X and Yuan Y: Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res. 36:112017. View Article : Google Scholar : PubMed/NCBI
19	Ruan W, Wang P, Feng S, Xue Y and Li Y: Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells. Tumour Biol. 37:4065–4073. 2016. View Article : Google Scholar : PubMed/NCBI
20	Lei W, Wang ZL, Feng HJ, Lin XD, Li CZ and Fan D: Long non-coding RNA SNHG12promotes the proliferation and migration of glioma cells by binding to HuR. Int J Oncol. 53:1374–1384. 2018.PubMed/NCBI
21	Ding S, Qu W, Jiao Y, Zhang J, Zhang C and Dang S: LncRNA SNHG12 promotes the proliferation and metastasis of papillary thyroid carcinoma cells through regulating wnt/beta-catenin signaling pathway. Cancer Biomark. 22:217–226. 2018. View Article : Google Scholar : PubMed/NCBI
22	Yang BF, Cai W and Chen B: LncRNA SNHG12 regulated the proliferation of gastric carcinoma cell BGC-823 by targeting microRNA-199a/b-5p. Eur Rev Med Pharmacol Sci. 22:1297–1306. 2018.PubMed/NCBI
23	Dong J, Wang Q, Li L and Xiao-Jin Z: Upregulation of long non-coding RNA small nucleolar RNA host gene 12 contributes to cell growth and invasion in cervical cancer by acting as a sponge for MiR-424-5p. Cell Physiol Biochem. 45:2086–2094. 2018. View Article : Google Scholar : PubMed/NCBI
24	Zhang H and Lu W: LncRNA SNHG12 regulates gastric cancer progression by acting as a molecular sponge of miR320. Mol Med Rep. 17:2743–2749. 2018.PubMed/NCBI
25	Wang O, Yang F, Liu Y, Lv L, Ma R, Chen C, Wang J, Tan Q, Cheng Y, Xia E, et al: C-MYC-induced upregulation of lncRNA SNHG12 regulates cell proliferation, apoptosis and migration in triple-negative breast cancer. Am J Transl Res. 9:533–545. 2017.PubMed/NCBI
26	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
27	Li Y, Sun Z, Liu B, Shan Y, Zhao L and Jia L: Tumor-suppressive miR-26a and miR-26b inhibit cell aggressiveness by regulating FUT4 in colorectal cancer. Cell Death Dis. 8:e28922017. View Article : Google Scholar : PubMed/NCBI
28	Lv H, Zhang Z, Wang Y, Li C, Gong W and Wang X: MicroRNA-92a promotes colorectal cancer cell growth and migration by inhibiting KLF4. Oncol Res. 23:283–290. 2016. View Article : Google Scholar
29	Qian J, Jiang B, Li M, Chen J and Fang M: Prognostic significance of microRNA-16 expression in human colorectal cancer. World J Surg. 37:2944–2949. 2013. View Article : Google Scholar : PubMed/NCBI
30	Ma Q, Wang X, Li Z, Li B, Ma F, Peng L, Zhang Y, Xu A and Jiang B: microRNA-16 represses colorectal cancer cell growth in vitro by regulating the p53/survivin signaling pathway. Oncol Rep. 29:1652–1658. 2013. View Article : Google Scholar : PubMed/NCBI
31	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
32	Wang P, Chen D, Ma H and Li Y: LncRNA SNHG12 contributes to multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small cell lung cancer. Oncotarget. 8:84086–84101. 2017.PubMed/NCBI
33	Wang X, Qi G, Zhang J, Wu J, Zhou N, Li L and Ma J: Knockdown of long noncoding RNA small nucleolar RNA host gene 12 inhibits cell growth and induces apoptosis by upregulating miR-138 in nonsmall cell lung cancer. DNA Cell Biol. 36:892–900. 2017. View Article : Google Scholar : PubMed/NCBI