Upregulation of microRNA-155 promotes the migration and invasion of colorectal cancer cells through the regulation of claudin-1 expression

Zhang,Guang-Jun; Xiao,Hua-Xu; Tian,Hong-Peng; Liu,Zuo-Liang; Xia,Shu-Sen; Zhou,Tong

doi:10.3892/ijmm.2013.1348

Upregulation of microRNA-155 promotes the migration and invasion of colorectal cancer cells through the regulation of claudin-1 expression

Authors:
- Guang-Jun Zhang
- Hua-Xu Xiao
- Hong-Peng Tian
- Zuo-Liang Liu
- Shu-Sen Xia
- Tong Zhou
View Affiliations

Affiliations: First Department of General Surgery, Institute of Hepatobiliary, Pancreatic and Intestinal Disease, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: April 15, 2013 https://doi.org/10.3892/ijmm.2013.1348
Pages: 1375-1380

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-155 (miR-155) has been demonstrated to regulate a variety of cellular functions, including epithelial-to-mesenchymal transition (EMT) by targeting multiple messenger RNAs (mRNAs). However, its role in colorectal cancer (CRC) remains unelucidated. Therefore, the aim of the present study was to investigate the effects of miR-155 on CRC cells. The expression level of miR-155 was quantified by quantitative real-time reverse transcriptase-PCR (qRT-PCR) in primary CRC tissues and normal adjacent mucosa. MTT, migration and invasion assays were used to examine the proliferation, migration and invasion of SW480 cells transfected with miR‑155. The expression of miR-155 was significantly upregulated in the CRC tissues and the high expression of miR-155 correlated with an advanced clinical stage, lymph node and distant metastases. The ectopic expression of miR-155 enhanced the migration and invasive ability of the SW480 cells and altered their morphological appearance; however, cell proliferation was not affected. E-cadherin expression levels decreased, while ZEB1 expression levels increased in the SW480 cells overexpressing miR-155. Furthermore, the overexpression of miR-155 upregulated claudin-1 expression. Thus, our data suggest that miR-155 plays an important role in promoting CRC cell migration and invasion, at least in part through the regulation of claudin-1 expression and controlling metastasis in CRC.

View Figures

View References

1	Jemal A, Siegel R, Ward E, et al: Cancer statistics. CA Cancer J Clin. 58:71–96. 2008.
2	Kobayashi H, Mochizuki H, Sugihara K, et al: Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 141:67–75. 2007. View Article : Google Scholar : PubMed/NCBI
3	Yang J and Weinberg RA: Epithelial-mesenchymal transition: at the crossroads of development and tumour metastasis. Dev Cell. 14:818–829. 2008. View Article : Google Scholar : PubMed/NCBI
4	Jou J and Diehl AM: Epithelial-mesenchymal transitions and hepatocarcinogenesis. J Clin Invest. 120:1031–1034. 2010. View Article : Google Scholar : PubMed/NCBI
5	Spaderna S, Schmalhofer O, Hlubek F, et al: A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology. 131:830–840. 2006. View Article : Google Scholar : PubMed/NCBI
6	Thiery JP: Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 15:740–746. 2003. View Article : Google Scholar : PubMed/NCBI
7	Eades G, Yao Y, Yang M, et al: miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells. J Biol Chem. 286:25992–26002. 2011. View Article : Google Scholar : PubMed/NCBI
8	Kurashige J, Kamohara H, Watanabe M, et al: MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma. Ann Surg Oncol. 19(Suppl 3): S656–S664. 2012. View Article : Google Scholar : PubMed/NCBI
9	Yang J, Mani SA, Donaher JL, et al: Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 117:927–939. 2004. View Article : Google Scholar : PubMed/NCBI
10	Eger A, Aigner K, Sonderegger S, et al: DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 24:2375–2385. 2005. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Zhang T, Liu M, Wang C, et al: Down-regulation of miR-206 promotes proliferation and invasion of laryngeal cancer by regulating VEGF expression. Anticancer Res. 31:3859–3863. 2011.PubMed/NCBI
13	Wu J, Wu G, Lv L, et al: MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1. Carcinogenesis. 33:519–528. 2012. View Article : Google Scholar : PubMed/NCBI
14	Gironella M, Seux M, Xie MJ, et al: Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155 and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA. 104:16170–16175. 2007. View Article : Google Scholar : PubMed/NCBI
15	Iorio MV, Ferracin M, Liu CG, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
16	Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
17	Shibuya H, Iinuma H, Shimada R, et al: Clinicopathological and prognostic value of microRNA-21 and microRNA-155 in colorectal cancer. Oncology. 79:313–320. 2010. View Article : Google Scholar : PubMed/NCBI
18	Kong W, Yang H, He L, et al: MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 28:6773–6784. 2008. View Article : Google Scholar : PubMed/NCBI
19	Bacac M and Stamenkovic I: Metastatic cancer cell. Annu Rev Pathol. 3:221–247. 2008. View Article : Google Scholar
20	Tsukita S and Furuse M: Claudin-based barrier in simple and stratified cellular sheets. Curr Opin Cell Biol. 14:531–536. 2002. View Article : Google Scholar : PubMed/NCBI
21	Ikari A, Takiguchi A, Atomi K, et al: Decrease in claudin-2 expression enhances cell migration in renal epithelial Madin-Darby canine kidney cells. J Cell Physiol. 226:1471–1478. 2011. View Article : Google Scholar : PubMed/NCBI
22	Yoon CH, Kim MJ, Park MJ, et al: Claudin-1 acts through c-Abl-protein kinase CI (PKCI) signaling and has a causal role in the acquisition of invasive capacity in human liver cells. J Biol Chem. 285:226–233. 2010. View Article : Google Scholar : PubMed/NCBI
23	Lee JW, Hsiao WT, Chen HY, et al: Up-regulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells. Int J Cancer. 126:1353–1366. 2010.PubMed/NCBI
24	Dhawan P, Singh AB, Deane NG, et al: Claudin-1 regulates cellular transformation and metastatic or in colon cancer. J Clin Invest. 115:1765–1776. 2005. View Article : Google Scholar : PubMed/NCBI
25	Kinugasa T, Akagi Y, Ochi T, et al: Increased claudin-1 protein expression in hepatic metastatic lesions of colorectal cancer. Anticancer Res. 32:2309–2314. 2012.PubMed/NCBI
26	Singh AB, Sharma A, Smith JJ, et al: Claudin-1 up-regulates the repressor ZEB-1 to inhibit E-cadherin expression in colon cancer cells. Gastroenterology. 141:2140–2153. 2011. View Article : Google Scholar : PubMed/NCBI