MiR-125a-5p Inhibits Colorectal Cancer Cell Epithelial-mesenchymal Transition, Invasion and Migration by Targeting TAZ

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Jun 14

PMID 31190857

Citations 17

Authors

Lei Tang

Li Zhou

Shengchun Wu

Xiaoming Shi

Guangwei Jiang

Shuai Niu

Dianzhu Ding

Affiliations

Soon will be listed here.

Abstract

miR-125a-5p regulated biological processes in various types of cancer, including colorectal cancer (CRC). TAZ, a vital transcriptional coactivators of the Hippo pathway, was found to be overexpressed in various cancers. This study aims to study the effect of miR-125a-5p on the progression of CRC by regulating TAZ expression. In this study, miR-125a-5p and TAZ expression in CRC tissue and cell lines were detected by real-time polymerase chain reaction (RT-PCR). Luciferase reporter assay was applied to detect whether TAZ was a target of miR-125a-5p. Cell migration and invasion were detected in vitro by wound-healing assay and cell invasion assay. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. The results revealed downregulation of miR-125a-5p, as well as upregulation of TAZ in CRC tissue and cell lines. TAZ was identified as a direct target of miR-125a-5p, and its expression was negatively regulated by miR-125a-5p in CRC cell lines. The functional studies revealed that overexpression of miR-125a-5p inhibited the migration, invasion and EMT of CRC cells, while upregulation of TAZ reversed the inhibitory effect caused by miR-125a-5p. Our data suggest that miR-125a-5p inhibits CRC cell migration, invasion and EMT by targeting TAZ. These results suggest that miR-125a-5p serves as a potential therapeutic biomarker for CRC patients.

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References

Hong J, Hwang E, McManus M, Amsterdam A, Tian Y, Kalmukova R . TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005; 309(5737):1074-8. DOI: 10.1126/science.1110955. View

Zhang B, Pan X, Cobb G, Anderson T . microRNAs as oncogenes and tumor suppressors. Dev Biol. 2006; 302(1):1-12. DOI: 10.1016/j.ydbio.2006.08.028. View

Chan S, Lim C, Guo K, Peng Ng C, Lee I, Hunziker W . A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells. Cancer Res. 2008; 68(8):2592-8. DOI: 10.1158/0008-5472.CAN-07-2696. View

Wang G, Mao W, Zheng S, Ye J . Epidermal growth factor receptor-regulated miR-125a-5p--a metastatic inhibitor of lung cancer. FEBS J. 2009; 276(19):5571-8. PMC: 2776928. DOI: 10.1111/j.1742-4658.2009.07238.x. View

Pan D . The hippo signaling pathway in development and cancer. Dev Cell. 2010; 19(4):491-505. PMC: 3124840. DOI: 10.1016/j.devcel.2010.09.011. View

Kim J, Noh J, Jung K, Eun J, Bae H, Kim M . Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b. Hepatology. 2012; 57(3):1055-67. DOI: 10.1002/hep.26101. View

Yuen H, McCrudden C, Huang Y, Tham J, Zhang X, Zeng Q . TAZ expression as a prognostic indicator in colorectal cancer. PLoS One. 2013; 8(1):e54211. PMC: 3553150. DOI: 10.1371/journal.pone.0054211. View

Siegel R, DeSantis C, Jemal A . Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014; 64(2):104-17. DOI: 10.3322/caac.21220. View

Van Cutsem E, Cervantes A, Nordlinger B, Arnold D . Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 Suppl 3:iii1-9. DOI: 10.1093/annonc/mdu260. View

10.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

11.

Wang Q, Xu Z, An Q, Jiang D, Wang L, Liang B . TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells. Mol Med Rep. 2014; 11(2):982-8. PMC: 4262480. DOI: 10.3892/mmr.2014.2818. View

12.

Yuan J, Xiao G, Peng G, Liu D, Wang Z, Liao Y . MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ. Biochem Biophys Res Commun. 2014; 457(2):171-6. DOI: 10.1016/j.bbrc.2014.12.078. View

13.

Cao H, Xu E, Liu H, Wan L, Lai M . Epithelial-mesenchymal transition in colorectal cancer metastasis: A system review. Pathol Res Pract. 2015; 211(8):557-69. DOI: 10.1016/j.prp.2015.05.010. View

14.

Tong Z, Liu N, Lin L, Guo X, Yang D, Zhang Q . miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer via targeting BCL2, BCL2L12 and MCL1. Biomed Pharmacother. 2015; 75:129-36. DOI: 10.1016/j.biopha.2015.07.036. View

15.

Xie D, Cui J, Xia T, Jia Z, Wang L, Wei W . Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression. Oncotarget. 2015; 6(34):35949-63. PMC: 4742153. DOI: 10.18632/oncotarget.5772. View

16.

Sun Y, Liu X, Zhang Q, Mao X, Feng L, Su P . Oncogenic potential of TSTA3 in breast cancer and its regulation by the tumor suppressors miR-125a-5p and miR-125b. Tumour Biol. 2015; 37(4):4963-72. DOI: 10.1007/s13277-015-4178-4. View

17.

Bhartiya D, Scaria V . Genomic variations in non-coding RNAs: Structure, function and regulation. Genomics. 2016; 107(2-3):59-68. DOI: 10.1016/j.ygeno.2016.01.005. View

18.

Yang R, Wu Y, Zou J, Zhou J, Wang M, Hao X . The Hippo transducer TAZ promotes cell proliferation and tumor formation of glioblastoma cells through EGFR pathway. Oncotarget. 2016; 7(24):36255-36265. PMC: 5094998. DOI: 10.18632/oncotarget.9199. View

19.

Malik S, Khan M, Dar M, Hussain M, Mudassar S . TAZ is an independent prognostic factor in non-small cell lung carcinoma: Elucidation at protein level. Cancer Biomark. 2017; 18(4):389-395. DOI: 10.3233/CBM-160263. View

20.

Cao Y, Tan S, Tu Y, Zhang G, Liu Y, Li D . MicroRNA-125a-5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression. Oncol Lett. 2018; 15(4):5119-5130. PMC: 5840665. DOI: 10.3892/ol.2018.7983. View