MicroRNA-141 inhibits migration of gastric cancer by targeting zinc finger E-box-binding homeobox 2

Du,Ying; Wang,Lingfei; Wu,Honghai; Zhang,Yiyin; Wang,Kan; Wu,Dingting

doi:10.3892/mmr.2015.3789

MicroRNA-141 inhibits migration of gastric cancer by targeting zinc finger E-box-binding homeobox 2

Authors:
- Ying Du
- Lingfei Wang
- Honghai Wu
- Yiyin Zhang
- Kan Wang
- Dingting Wu
View Affiliations

Affiliations: Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Institute of Pharmacology and Toxicology, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China, Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
Published online on: May 15, 2015 https://doi.org/10.3892/mmr.2015.3789
Pages: 3416-3422
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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

Human microRNA (miR)-141 is a member of the miR‑200 family, which has been reported to be downregulated in gastric cancer, and involved in the proliferation of gastric cancer cells. However, little is currently known regarding its role in the migration of gastric cancer. The present study investigated the function of miR‑141 in gastric cancer cell migration, and evaluated the contribution of zinc finger E‑box‑binding homeobox 1 and 2 (ZEB1/2) in miR‑141 mediated migration of gastric cancer cells. The expression levels of miR‑141 and its potential ZEB1/2 targets were examined by quantitative polymerase chain reaction (qPCR) and western blotting, respectively. The migration of SGC‑7901 and HGC‑27 gastric cancer cells, which had been transfected with an miRNA precursor, was examined by cell migration and wound healing assays. A luciferase activity assay was used to validate whether ZEB1/2 was a direct target of miR‑141. The results demonstrated that overexpression of miR‑141 markedly inhibited the migration of gastric cancer cells in vitro. Forced overexpression of miR‑141 significantly reduced the luciferase activity of the 3'‑untranslated region of ZEB2 in gastric cancer cells. Furthermore, the mRNA and protein expression levels of ZEB2 were reduced in cells overexpressing miR‑141, whereas the protein expression levels of E‑cadherin were increased. In gastric tumor samples the expression levels of ZEB2 were inversely correlated with the expression of miR‑141. These results suggest that miR‑141 may be involved in the inhibition of gastric cancer cell migration, and that ZEB2 is a target gene of miR-141.

View Figures

View References

1	Shen L, Shan YS, Hu HM, et al: Management of gastric cancer in Asia: Resource-stratified guidelines. Lancet Oncol. 14:e535–e547. 2013. View Article : Google Scholar : PubMed/NCBI
2	Thrumurthy SG, Chaudry MA, Hochhauser D and Mughal M: The diagnosis and management of gastric cancer. BMJ. 347:f63672013. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
4	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI
5	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
6	Zhang X, Nie Y, Du Y, Cao J, Shen B and Li Y: MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6. Tumour Biol. 33:1589–1597. 2012. View Article : Google Scholar : PubMed/NCBI
7	Ding L, Xu Y, Zhang W, et al: MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res. 20:784–793. 2010. View Article : Google Scholar : PubMed/NCBI
8	Du Y, Xu Y, Ding L, et al: Down-regulation of miR-141 in gastric cancer and its involvement in cell growth. J Gastroenterol. 44:556–561. 2009. View Article : Google Scholar : PubMed/NCBI
9	Hu M, Xia M, Chen X, et al: MicroRNA-141 regulates Smad interacting protein 1 (SIP1) and inhibits migration and invasion of colorectal cancer cells. Dig Dis Sci. 55:2365–2372. 2010. View Article : Google Scholar
10	Liu Y, Ding Y, Huang J, et al: MiR-141 suppresses the migration and invasion of HCC cells by targeting Tiam1. PLoS One. 9:e883932014. View Article : Google Scholar : PubMed/NCBI
11	Xu L, Li Q, Xu D, et al: hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and migration. Int J Oncol. 44:459–466. 2014.
12	Gregory PA, Bracken CP, Bert AG and Goodall GJ: MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle. 7:3112–3118. 2008. View Article : Google Scholar : PubMed/NCBI
13	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
14	Korpal M, Lee ES, Hu G and Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 283:14910–14914. 2008. View Article : Google Scholar : PubMed/NCBI
15	Nakada C, Matsuura K, Tsukamoto Y, et al: Genome-wide microRNA expression profiling in renal cell carcinoma: Significant down-regulation of miR-141 and miR-200c. J Pathol. 216:418–427. 2008. View Article : Google Scholar : PubMed/NCBI
16	Tamagawa S, Beder LB, Hotomi M, et al: Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma. Int J Mol Med. 33:879–886. 2014.PubMed/NCBI
17	Zhou T, Zimmerman W, Liu X and Erikson RL: A mammalian NudC-like protein essential for dynein stability and cell viability. Proc Natl Acad Sci USA. 103:9039–9044. 2006. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(2Delta Delta C (T)). Method Methods. 25:402–408. 2001. View Article : Google Scholar
19	Song S and Ajani JA: The role of microRNAs in cancers of the upper gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 10:109–118. 2013. View Article : Google Scholar
20	Zhao G, Wang B, Liu Y, et al: miRNA-141, downregulated in pancreatic cancer, inhibits cell proliferation and invasion by directly targeting MAP4K4. Mol Cancer Ther. 12:2569–2580. 2013. View Article : Google Scholar : PubMed/NCBI
21	Chen B, Huang T, Jiang J, Lv L, Li H and Xia S: miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF. Mol Cell Biochem. 388:211–218. 2014. View Article : Google Scholar
22	Larue L and Bellacosa A: Epithelial-mesenchymal transition in development and cancer: Role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene. 24:7443–7454. 2005. View Article : Google Scholar : PubMed/NCBI
23	Gregory PA, Bert AG, Paterson EL, et al: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 10:593–601. 2008. View Article : Google Scholar : PubMed/NCBI
24	Peinado H, Olmeda D and Cano A: Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype? Nat Rev Cancer. 7:415–428. 2007. View Article : Google Scholar : PubMed/NCBI
25	Wu SM, Ai HW, Zhang DY, et al: MiR-141 targets ZEB2 to suppress HCC progression. Tumour Biol. 35:9993–9997. 2014. View Article : Google Scholar : PubMed/NCBI