MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancerReportar como inadecuado




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Molecular Cancer

, 11:23

First Online: 25 April 2012Received: 29 December 2011Accepted: 25 April 2012

Abstract

BackgroundMicroRNAs miRNAs have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 MACC1 has been newly identified to express highly in colorectal cancer CRC and promote tumor metastasis through transactivating metastasis-inducing HGF-MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.

ResultsUsing both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3- UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.

ConclusionsOur findings newly described miR-143-MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.

KeywordsmiR-143 MACC1 Colorectal cancer Invasion Migration AbbreviationsmiRmicroRNA

CRCcolorectal cancer

MACC1metastasis-associated in colon cancer-1

3-UTR3- untranslated regions.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-11-23 contains supplementary material, which is available to authorized users.

Yu Zhang, Zhongqiu Wang contributed equally to this work.

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Autor: Yu Zhang - Zhongqiu Wang - Min Chen - Liang Peng - Xinying Wang - Qunying Ma - Fengli Ma - Bo Jiang

Fuente: https://link.springer.com/article/10.1186/1476-4598-11-23







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