miR‑203a suppresses cell proliferation by targeting E2F transcription factor 3 in human gastric cancer

Yang,Huiqin; Wang,Lixia; Tang,Xiaoli; Bai,Wenmei

doi:10.3892/ol.2017.7199

miR‑203a suppresses cell proliferation by targeting E2F transcription factor 3 in human gastric cancer

Authors:
- Huiqin Yang
- Lixia Wang
- Xiaoli Tang
- Wenmei Bai
View Affiliations

Affiliations: Respiratory Department, Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region 830016, P.R. China
Published online on: October 17, 2017 https://doi.org/10.3892/ol.2017.7199
Pages: 7687-7690

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

MicroRNAs (miRs) are a class of short non‑coding RNAs that serve an essential role in the tumorigenesis of gastric cancer (GC). MiR‑203a has been reported as a tumor repressor in various types of human cancer. In the present study, the function of miR‑203a on the proliferation of GC cells was investigated. Bioinformatics analyses revealed that miR‑203a targets the 3'‑untranslated region of E2F transcription factor 3 (E2F3) messenger RNA. A luciferase reporter assay and western blot analysis were performed to confirm whether E2F3 was a target of miR‑203a. The relative luciferase activity was decreased when overexpressing miR‑203a with E2F3‑wild type pmirGLO‑3'‑untranslated region vector, compared with the control group in HEK293 cells. Overexpression of miR‑203a suppressed cell proliferation and colony formation of SGC‑7901 and AGS GC cells. Inhibition of miR‑203a promoted the proliferation of GC cells. Collectively, the results indicated that miR‑203a may function as a tumor suppressor in GC by targeting E2F3.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Dassen A, Lemmens VE, van de Poll-Franse LV, Creemers GJ, Brenninkmeijer SJ, Lips DJ, Wurff Vd AA, Bosscha K and Coebergh JW: Trends in incidence, treatment and survival of gastric adenocarcinoma between 1990 and 2007: A population-based study in the Netherlands. Eur J Cancer. 46:1101–1110. 2010. View Article : Google Scholar : PubMed/NCBI
3	Wu HH, Lin WC and Tsai KW: Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Rev Mol Med. 16:e12014. View Article : Google Scholar : PubMed/NCBI
4	Kim SJ, Wang YG, Lee HW, Kang HG, La SH, Choi IJ, Irimura T, Ro JY, Bresalier RS and Chun KH: Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer. Oncotarget. 5:3386–3398. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ohtsu A: Chemotherapy for metastatic gastric cancer: Past, present, and future. J Gastroenterol. 43:256–264. 2008. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Wienholds E and Plasterk RH: MicroRNA function in animal development. FEBS Lett. 579:5911–5922. 2005. View Article : Google Scholar : PubMed/NCBI
8	He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
9	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
10	Shah PP, Hutchinson LE and Kakar SS: Emerging role of microRNAs in diagnosis and treatment of various diseases including ovarian cancer. J Ovarian Res. 2:112009. View Article : Google Scholar : PubMed/NCBI
11	Liu Y, Dong Z, Liang J, Guo Y, Guo X, Shen S, Kuang G and Guo W: Methylation-mediated repression of potential tumor suppressor miR-203a and miR-203b contributes to esophageal squamous cell carcinoma development. Tumour Biol. 37:5621–5632. 2016. View Article : Google Scholar : PubMed/NCBI
12	Liu D, Wu J, Liu M, Yin H, He J and Zhang B: Downregulation of miRNA-30c and miR-203a is associated with hepatitis C virus core protein-induced epithelial-mesenchymal transition in normal hepatocytes and hepatocellular carcinoma cells. Biochem Biophys Res Commun. 464:1215–1221. 2015. View Article : Google Scholar : PubMed/NCBI
13	Lin QH, Zhang KD, Duan HX, Liu MX, Wei WL and Cao Y: ERGIC3, which is regulated by miR-203a, is a potential biomarker for non-small cell lung cancer. Cancer Sci. 106:1463–1473. 2015. View Article : Google Scholar : PubMed/NCBI
14	Kara M, Yumrutas O, Ozcan O, Celik OI, Bozgeyik E, Bozgeyik I and Tasdemir S: Differential expressions of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma. Gene. 567:81–86. 2015. View Article : Google Scholar : PubMed/NCBI
15	Yang Y, Chang S, Zhao Z, et al: MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3. Oncol Lett. 10:3779–3784. 2015.PubMed/NCBI
16	Julian LM, Vandenbosch R, Pakenham CA, Andrusiak MG, Nguyen AP, McClellan KA, Svoboda DS, Lagace DC, Park DS, Leone G, et al: Opposing regulation of Sox2 by cell-cycle effectors E2f3a and E2f3b in neural stem cells. Cell Stem Cell. 12:440–452. 2013. View Article : Google Scholar : PubMed/NCBI
17	Sharma N, Timmers C, Trikha P, Saavedra HI, Obery A and Leone G: Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S progression and cellular transformation. J Biol Chem. 281:36124–36131. 2006. View Article : Google Scholar : PubMed/NCBI
18	Li X, Li H, Zhang R and Liu J and Liu J: MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing E2F3 in gastric cancer. Cell Physiol Biochem. 35:2033–2042. 2015. View Article : Google Scholar : PubMed/NCBI
19	Oeggerli M, Tomovska S, Schraml P, Calvano-Forte D, Schafroth S, Simon R, Gasser T, Mihatsch MJ and Sauter G: E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. Oncogene. 23:5616–5623. 2004. View Article : Google Scholar : PubMed/NCBI
20	Miles WO, Tschop K, Herr A, Ji JY and Dyson NJ: Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes Dev. 26:356–368. 2012. View Article : Google Scholar : PubMed/NCBI
21	Wiemer EA: The role of microRNAs in cancer: No small matter. Eur J Cancer. 43:1529–1544. 2007. View Article : Google Scholar : PubMed/NCBI
22	Lee SA, Kim JS, Park SY, Kim HJ, Yu SK, Kim CS, Chun HS, Kim J, Park JT, Go D, et al: miR-203 downregulates Yes-1 and suppresses oncogenic activity in human oral cancer cells. J Biosci Bioeng. 120:351–358. 2015. View Article : Google Scholar : PubMed/NCBI
23	Xu L, Shen B, Chen T and Dong P: miR-203 is involved in the laryngeal carcinoma pathogenesis via targeting VEGFA and Cox-2. Onco Targets Ther. 9:4629–4637. 2016. View Article : Google Scholar : PubMed/NCBI
24	Hu G, Lai P, Liu M, Xu L, Guo Z, Liu H, Li W, Wang G, Yao X, Zheng J, et al: miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen synthase kinase-3β in human renal cell carcinoma. Tumour Biol. 35:11443–11453. 2014. View Article : Google Scholar : PubMed/NCBI
25	Wang L, Sun H, Wang X, Hou N, Zhao L, Tong D, He K, Yang Y, Song T, Yang J, et al: EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway. Oncotarget. 7:45302–45316. 2016. View Article : Google Scholar : PubMed/NCBI
26	Wang C, Wang X, Liang H, Wang T, Yan X, Cao M, Wang N, Zhang S, Zen K, Zhang C, et al: miR-203 inhibits cell proliferation and migration of lung cancer cells by targeting PKCα. PloS One. 8:e739852013. View Article : Google Scholar : PubMed/NCBI