Long non‑coding RNA DLX6‑AS1 silencing inhibits malignant phenotypes of gastric cancer cells

Fu,Xiaodan; Tian,Yifu; Kuang,Weilu; Wen,Sailan; Guo,Wei

doi:10.3892/etm.2019.7521

Long non‑coding RNA DLX6‑AS1 silencing inhibits malignant phenotypes of gastric cancer cells

Authors:
- Xiaodan Fu
- Yifu Tian
- Weilu Kuang
- Sailan Wen
- Wei Guo
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Affiliations: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410005, P.R. China, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410005, P.R. China, Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Pathology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410002, P.R. China
Published online on: April 23, 2019 https://doi.org/10.3892/etm.2019.7521
Pages: 4715-4722

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Abstract

It has been revealed that long non‑coding RNAs (lncRNAs) serve a key role in various malignancies, including gastric cancer (GC). In the present study, the expression and function of lncRNA distal‑less homeobox 6 antisense 1 (DLX6‑AS1) in GC was investigated. The data revealed that the expression of DLX6‑AS1 was significantly upregulated in GC tissues compared with adjacent paired noncancerous tissues. Furthermore, the expression of DLX6‑AS1 was higher in advanced GC tissue samples (III/IV) compared with the expression in early‑stage samples (I/II). Furthermore, the current study demonstrated that a high expression of DLX6‑AS1 was significantly associated with advanced clinical stage, lymph node metastasis and distant metastasis. Compared with patients with a low DLX6‑AS1 expression, DLX6‑AS1 expression in patients with GC was associated with decreased survival. In vitro experimental data indicated that DLX6‑AS1 was upregulated in GC cell lines and that the inhibition of DLX6‑AS1 markedly reduced GC cell proliferation, colony formation, cell cycle progression, migration and invasion. Further investigation revealed that knockdown of DLX6‑AS1 inhibited EMT in GC cells. In summary, the present study demonstrated that lncRNA DLX6‑AS1 was upregulated and serves an oncogenic role in GC, indicating that DLX6‑AS1 may be a novel therapeutic target for GC treatment.

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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	Röcken C: Molecular classification of gastric cancer. Expert Rev Mol Diagn. 17:293–301. 2017. View Article : Google Scholar : PubMed/NCBI
4	Silva A, Bullock M and Calin G: The clinical relevance of long non-coding RNAs in cancer. Cancers (Basel). 7:2169–2182. 2015. View Article : Google Scholar : PubMed/NCBI
5	Hung T and Chang HY: Long noncoding RNA in genome regulation: Prospects and mechanisms. RNA Biol. 7:582–585. 2010. View Article : Google Scholar : PubMed/NCBI
6	Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI
7	Clark MB and Mattick JS: Long noncoding RNAs in cell biology. Semin Cell Dev Biol. 22:366–376. 2011. View Article : Google Scholar : PubMed/NCBI
8	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/ß-catenin signaling pathway. Cell Physiol Biochem. 46:1275–1285. 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 Mol Basis Dis. 1864:2871–2880. 2018. View Article : Google Scholar : PubMed/NCBI
10	Li PF, Chen SC, Xia T, Jiang XM, Shao YF, Xiao BX and Guo JM: Non-coding RNAs and gastric cancer. World J Gastroenterol. 20:5411–5419. 2014. View Article : Google Scholar : PubMed/NCBI
11	Gibb EA, Brown CJ and Lam WL: The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10:382011. View Article : Google Scholar : PubMed/NCBI
12	Xu R, Zhu X, Chen F, Huang C, Ai K, Wu H, Zhang L and Zhao X: LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells. Cancer Cell Int. 18:412018. View Article : Google Scholar : PubMed/NCBI
13	Xiong W, Huang C, Deng H, Jian C, Zen C, Ye K, Zhong Z, Zhao X and Zhu L: Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through the SRC3/IGF1R/AKT pathway. Int J Biochem Cell Biol. 94:125–132. 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	Zhang Q, Chen B, Liu P and Yang J: XIST promotes gastric cancer (GC) progression through TGF-beta1 via targeting miR-185. J Cell Biochem. 119:2787–2796. 2018. View Article : Google Scholar : PubMed/NCBI
16	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
17	Li J, Li P, Zhao W, Yang R, Chen S, Bai Y, Dun S, Chen X, Du Y, Wang Y, et al: Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma. Cancer Cell Int. 15:482015. View Article : Google Scholar : PubMed/NCBI
18	Zeng X, Hu Z, Ke X, Tang H, Wu B, Wei X and Liu Z: Long noncoding RNA DLX6-AS1 promotes renal cell carcinoma progression via miR-26a/PTEN axis. Cell Cycle. 16:2212–2219. 2017. View Article : Google Scholar : PubMed/NCBI
19	Zhang L, He X, Jin T, Gang L and Jin Z: Long non-coding RNA DLX6-AS1 aggravates hepatocellular carcinoma carcinogenesis by modulating miR-203a/MMP-2 pathway. Biomed Pharmacother. 96:884–891. 2017. View Article : Google Scholar : PubMed/NCBI
20	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
21	Lim S and Kaldis P: Cdks, cyclins and CKIs: Roles beyond cell cycle regulation. Development. 140:3079–3093. 2013. View Article : Google Scholar : PubMed/NCBI
22	Mowers EE, Sharifi MN and Macleod KF: Functions of autophagy in the tumor microenvironment and cancer metastasis. FEBS J. 285:1751–1766. 2018. View Article : Google Scholar : PubMed/NCBI
23	Luo J, Chen J, Li H, Yang Y, Yun H, Yang S and Mao X: LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR-143/HMGB1 pathway. Oncol Lett. 14:5556–5562. 2017.PubMed/NCBI
24	Zhu H, Zheng T, Yu J, Zhou L and Wang L: LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a. Biomed Pharmacother. 105:789–797. 2018. View Article : Google Scholar : PubMed/NCBI
25	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
26	Kahroba H, Hejazi MS and Samadi N: Exosomes: From carcinogenesis and metastasis to diagnosis and treatment of gastric cancer. Cell Mol Life Sci. Feb 8–2019.Doi: 10.1007/s00018-019-03035-2. View Article : Google Scholar : PubMed/NCBI
27	Tan HY, Wang C, Liu G and Zhou X: Long noncoding RNA NEAT1-modualted miR-506 regulates gastric cancer development through targeting STAT3. J Cell Biochem. 120:4827–4836. 2018. View Article : Google Scholar
28	Ren K, Liu QQ, An ZF, Zhang DP and Chen XH: MiR-144 functions as tumor suppressor by targeting PIM1 in gastric cancer. Eur Rev Med Pharmacol Sci. 21:3028–3037. 2017.PubMed/NCBI
29	Liu J, Liu L, Wan JX and Song Y: Long noncoding RNA SNHG20 promotes gastric cancer progression by inhibiting p21 expression and regulating the GSK-3beta/beta-catenin signaling pathway. Oncotarget. 8:80700–80708. 2017.PubMed/NCBI
30	Chen Z, Liu H, Yang H, Gao Y, Zhang G and Hu J: The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in gastric cancer. Onco Targets Ther. 10:3353–3362. 2017. View Article : Google Scholar : PubMed/NCBI
31	Fu JW, Kong Y and Sun X: Long noncoding RNA NEAT1 is an unfavorable prognostic factor and regulates migration and invasion in gastric cancer. J Cancer Res Clin Oncol. 142:1571–1579. 2016. View Article : Google Scholar : PubMed/NCBI
32	Ye Y, Xiao Y, Wang W, Yearsley K, Gao JX, Shetuni B and Barsky SH: ERalpha signaling through slug regulates E-cadherin and EMT. Oncogene. 29:1451–1462. 2010. View Article : Google Scholar : PubMed/NCBI
33	Xia XL, Xue D, Xiang TH, Xu HY, Song DK, Cheng PG and Wang JQ: Overexpression of long non-coding RNA CRNDE facilitates epithelial-mesenchymal transition and correlates with poor prognosis in intrahepatic cholangiocarcinoma. Oncol Lett. 15:4105–4112. 2018.PubMed/NCBI
34	Li C, Wan L, Liu Z, Xu G, Wang S, Su Z, Zhang Y, Zhang C, Liu X, Lei Z and Zhang HT: Long non-coding RNA XIST promotes TGF-beta-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett. 418:185–195. 2018. View Article : Google Scholar : PubMed/NCBI
35	Jia L, Tian Y, Chen Y and Zhang G: The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/beta-Catenin pathway. Onco Targets Ther. 11:313–321. 2018. View Article : Google Scholar : PubMed/NCBI