Colorectal Cancer Migration and Invasion Initiated by microRNA-106a

Bo Feng,Lin Lin Wang,Feng Dong,Hong Chao Zhao,Hou Min Zhou,Tao Tao Dong,Min Hua Zheng,Natasha Kyprianou

doi:10.1371/journal.pone.0043452

Abstract

MicroRNAs have been implicated in the regulation of several cellular signaling pathways of colorectal cancer (CRC) cells. Although emerging evidence proves that microRNA (miR)-106a is expressed highly in primary tumor and stool samples of CRC patients; whether or not miR-106a mediates cancer metastasis is unknown. We show here that miR-106a is highly expressed in metastatic CRC cells, and regulates cancer cell migration and invasion positively in vitro and in vivo. These phenotypes do not involve confounding influences on cancer cell proliferation. MiR-106a inhibits the expression of transforming growth factor-β receptor 2 (TGFBR2), leading to increased CRC cell migration and invasion. Importantly, miR-106a expression levels in primary CRCs are correlated with clinical cancer progression. These observations indicate that miR-106a inhibits the anti-metastatic target directly and results in CRC cell migration and invasion.

Highlights

Metastases lead to approximately 90% of colorectal cancer (CRC)-related mortalities, yet the underlying mechanisms remain largely unclear [1]
Results miR-106a is Highly Expressed in Metastatic CRC Cells We first determined the levels of miR-106a expression in a variety of human CRC cells
epithelial-mesenchymal transition (EMT) can be considered a pathologic process that contributes to cancer progression, as it relates to invasion and metastasis

Summary

Introduction

Metastases lead to approximately 90% of colorectal cancer (CRC)-related mortalities, yet the underlying mechanisms remain largely unclear [1]. Multiple studies have been conducted to investigate the genes and their products that are involved in metastasis [3,4,5,6,7]. The role for miRNAs in the establishment and progression of CRC has become evident. Greater than 50% of miRNA genes are situated in fragile chromosomal regions that are altered during tumor progression [9], and some miRNAs have been identified as oncogenes or tumor suppressor genes in CRC [10,11,12,13,14]. Expression profiling analysis has revealed characteristic miRNA signatures that can predict the clinical outcomes of CRC [15,16]

Methods

Results

Conclusion