lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer

Wang,Shimei; Zhu,Wei; Qiu,Ji; Chen,Fei

doi:10.3892/mmr.2020.11724

lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer

Authors:
- Shimei Wang
- Wei Zhu
- Ji Qiu
- Fei Chen
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Affiliations: Department of Gastroenterology, Zhuji People's Hospital of Zhejiang Province, Shaoxing, Zhejiang 311800, P.R. China, Department of General Surgery, Zhuji Central Hospital, Shaoxing, Zhejiang 311800, P.R. China
Published online on: November 23, 2020 https://doi.org/10.3892/mmr.2020.11724
Article Number: 85
Copyright: © Wang 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)RNAs and microRNAs (miRNAs/miRs) have physiological and pathological functions in various diseases, including gastric cancer (GC). The current study explored the association between lncRNA small nucleolar RNA host gene 4 (SNHG4) and miR‑148a‑3p, and their functions in GC cells. SNHG4 expression and overall survival data were analyzed using bioinformatics, and the interaction of SNHG4 and miR‑148a‑3p was predicted using starBase and confirmed via a dual‑luciferase reporter assay. Cell viability, colony formation ability and apoptosis rate were detected using Cell Counting Kit‑8, colony formation and flow cytometry assays, respectively. Cell migration and invasion were determined via wound‑healing and Transwell assays. mRNA and protein expression levels were determined via reverse transcription‑quantitative PCR and western blotting. The results demonstrated that in GC tissues and cell lines, SNHG4 was highly expressed, while miR‑204‑5p expression was decreased, and that the expression levels of SNHG4 and miR‑204‑5p were negatively correlated. The downregulated expression of SNHG4 decreased the effects of miR‑204‑5p inhibitor on promoting cell proliferation, migration, invasion and epithelial‑mesenchymal transition, but enhanced the inhibitory effect of miR‑204‑5p on GC cell apoptosis. The findings of the current study revealed the potential mechanism of the SNHG4‑miR‑204‑5p pathway in GC, which may be conducive to the development of novel drugs against GC growth.

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1	Van Cutsem E, Sagaert X, Topal B, Haustermans K and Prenen H: Gastric cancer. Lancet. 388:2654–2664. 2016. View Article : Google Scholar
2	Cai J, Niu X, Chen Y, Hu Q, Shi G, Wu H, Wang J and Yi J: Emodin-induced generation of reactive oxygen species inhibits RhoA activation to sensitize gastric carcinoma cells to anoikis. Neoplasia. 10:41–51. 2008. View Article : Google Scholar
3	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar
4	Sun Y and Ma L: The emerging molecular machinery and therapeutic targets of metastasis. Trends Pharmacol Sci. 36:349–359. 2015. View Article : Google Scholar
5	Turajlic S and Swanton C: Metastasis as an evolutionary process. Science. 352:169–175. 2016. View Article : Google Scholar
6	Tanabe S, Ishido K, Matsumoto T, Kosaka T, Oda I, Suzuki H, Fujisaki J, Ono H, Kawata N, Oyama T, et al: Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: A multicenter collaborative study. Gastric Cancer. 20 (Suppl 1):45–52. 2017. View Article : Google Scholar
7	Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al ToGA Trial Investigators, : Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar
8	Kang YK, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yoshikawa T, et al: Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): a double-blinded, randomized, phase III trial. J Clin Oncol. 35 (Suppl 4):2. 2017. View Article : Google Scholar
9	Xu X, Qian LJ, Su XY, He KF, Jin KT, Gu LH, Feng JG, Li GL, Zhou Q, Xu ZZ, et al: Establishment and characterization of GCSR1, a multi-drug resistant signet ring cell gastric cancer cell line. Int J Oncol. 46:2479–2487. 2015. View Article : Google Scholar
10	Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, et al: Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science. 308:1149–1154. 2005. View Article : Google Scholar
11	Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, et al Children's Hospital Oakland Research Institute, : Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 447:799–816. 2007. View Article : Google Scholar
12	Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, et al Consortium F; RIKEN Genome Exploration Research Group and Genome Science Group, : (Genome Network Project Core Group) The transcriptional landscape of the mammalian genome. Science. 309:1559–1563. 2005. View Article : Google Scholar
13	Geisler S and Coller J: RNA in unexpected places: Long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol. 14:699–712. 2013. View Article : Google Scholar
14	Hirakata S and Siomi MC: piRNA biogenesis in the germline: From transcription of piRNA genomic sources to piRNA maturation. Biochim Biophys Acta. 1859:82–92. 2016. View Article : Google Scholar
15	Jacquier A: The complex eukaryotic transcriptome: Unexpected pervasive transcription and novel small RNAs. Nat Rev Genet. 10:833–844. 2009. View Article : Google Scholar
16	Kim VN, Han J and Siomi MC: Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 10:126–139. 2009. View Article : Google Scholar
17	Clark MB, Choudhary A, Smith MA, Taft RJ and Mattick JS, Taft RJ and Mattick JS: The dark matter rises: The expanding world of regulatory RNAs. Essays Biochem. 54:1–16. 2013. View Article : Google Scholar
18	Li H, Hong J and Wijayakulathilaka WS: Long non-coding RNA SNHG4 promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p. Cell Cycle. 18:3313–3324. 2019. View Article : Google Scholar
19	Chen X, Chen Z, Yu S, Nie F, Yan S, Ma P, Chen Q, Wei C, Fu H, Xu T, et al: Long noncoding RNA LINC01234 functions as a competing endogenous RNA to regulate CBFB expression by sponging miR-204-5p in gastric cancer. Clin Cancer Res. 24:2002–2014. 2018. View Article : Google Scholar
20	In H, Solsky I, Palis B, Langdon-Embry M, Ajani J and Sano T: Validation of the 8th edition of the AJCC TNM staging system for gastric cancer using the national cancer database. Ann Surg Oncol. 24:3683–3691. 2017. View Article : Google Scholar
21	Nagy Á, Lánczky A, Menyhárt O and Győrffy B: Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 8:92272018. View Article : Google Scholar
22	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
23	Guarino M: Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol. 39:2153–2160. 2007. View Article : Google Scholar
24	Romeo E, Caserta CA, Rumio C and Marcucci F: The vicious cross-talk between tumor cells with an EMT phenotype and cells of the immune system. Cells. 8:82019. View Article : Google Scholar
25	Thiery JP: Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 15:740–746. 2003. View Article : Google Scholar
26	Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y and Johnson KR: Cadherin switching. J Cell Sci. 121:727–735. 2008. View Article : Google Scholar
27	Nishizuka M, Komada R and Imagawa M: Knockdown of RhoE expression enhances TGF-β-induced EMT (epithelial-to-mesenchymal transition) in cervical cancer HeLa cells. Int J Mol Sci. 20:202019. View Article : Google Scholar
28	Zhou J, Cheng H, Wang Z, Chen H, Suo C, Zhang H, Zhang J, Yang Y, Geng L, Gu M, et al: Bortezomib attenuates renal interstitial fibrosis in kidney transplantation via regulating the EMT induced by TNF-α-Smurf1-Akt-mTOR-P70S6K pathway. J Cell Mol Med. 23:5390–5402. 2019. View Article : Google Scholar
29	Xu R, Feng F, Yu X, Liu Z and Lao L: LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma. Cell Prolif. 51:e125152018. View Article : Google Scholar
30	Tang Y, Wu L, Zhao M, Zhao G, Mao S, Wang L, Liu S and Wang X: LncRNA SNHG4 promotes the proliferation, migration, invasiveness, and epithelial-mesenchymal transition of lung cancer cells by regulating miR-98-5p. Biochem Cell Biol. 97:767–776. 2019. View Article : Google Scholar
31	Bian Z, Jin L, Zhang J, Yin Y, Quan C, Hu Y, Feng Y, Liu H, Fei B, Mao Y, et al: LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p. Sci Rep. 6:238922016. View Article : Google Scholar
32	Yin Y, Zhang B, Wang W, Fei B, Quan C, Zhang J, Song M, Bian Z, Wang Q, Ni S, et al: miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A. Clin Cancer Res. 20:6187–6199. 2014. View Article : Google Scholar
33	Liu L, Wang J, Li X, Ma J, Shi C, Zhu H, Xi Q, Zhang J, Zhao X and Gu M: MiR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma. Biochem Biophys Res Commun. 457:621–626. 2015. View Article : Google Scholar