Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-α induced epithelial-to-mesenchymal transition in colorectal cancer.

Lanlan Huang,Junxiong Chen,Xiaoyan Wang,Huanliang Liu,Jianping Wang,Chenliang Wang,Bo Zhang,Lei Wang,Chuangyu Wen,Minmin Song,Xiangling Yang,Aikichi Iwamoto

doi:10.1038/srep13350

Abstract

Lymph node metastasis is an important factor determining the outcome of colorectal cancer. Although epithelial-to-mesenchymal transition (EMT), TNF-α and microRNA (miRNA) have been found to play important roles in lymph node metastasis, the underlying molecular mechanism remains unclear. Here we reported that high expression of microRNA-19a (miR-19a) was associated with lymph node metastasis and played an important role in TNF-α-induced EMT in colorectal cancer (CRC) cells. We analyzed miR-19a expression in surgical tissue specimens from 11 CRC patients and 275 formalin-fixed, paraffin-embedded CRC patients. We found that miR-19a was up-regulated in CRC tissues and high expression of miR-19a was significantly associated with lymph node metastasis. We further analyzed miR-19a lymph node metastasis signature in an external validation cohort of 311 CRC cases of the TCGA. MiR-19a was found to be significantly associated with lymph node metastasis in rectal cancer. In vitro, we showed that overexpression of miR-19a in human CRC cell lines promoted cell invasion and EMT. Furthermore, miR-19a was up-regulated by TNF-α and miR-19a was required for TNF-α-induced EMT and metastasis in CRC cells. Collectively, miR-19a played an important role in mediating EMT and metastatic behavior in CRC. It may serve as a potential marker of lymph node metastasis.

Highlights

IntroductionStudies reported that miR-19a promoted the proliferation and metastasis in colon cancer and cervical carcinoma[14,16]
We found that miR-19a was frequently up-regulated in Colorectal cancer (CRC) tissues and a high expression of miR19a was associated with lymph node metastasis
We demonstrated that miR-19a expression correlated with reduced E-cadherin and increased N-cadherin, Vimentin and Fibronectin expression in CRC cells

Summary

Introduction

Studies reported that miR-19a promoted the proliferation and metastasis in colon cancer and cervical carcinoma[14,16] These data suggested a potential function of miR-19a in carcinogenesis[12,13,14,15,16,17]. During EMT, epithelial tumor cells lose their epithelial morphology and gain of mesenchymal markers, which promote increased motility and invasiveness[18]. We reported that miR-19a was up-regulated in CRC tissue and high expression of miR-19a was significantly associated with lymph node metastasis. MiR-19a may act as a molecular marker for lymph node metastasis in CRC patients and mediate TNF-α induced EMT of CRC cells

Methods

Results

Conclusion