MiR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts.

Xiaodong Yang,Junjia Zhu,Xiaohui Xu,Kui Zhao,Chungen Xing,Yongyou Wu,Hong Zhu,Yong Wu,Shuyu Zhang,Wei Peng,Zhenyu Ye,Ming Li,Jianping Cao

doi:10.18632/oncotarget.12873

Abstract

Autophagy is a double-edged sword in tumor development. Recent studies have found that miRNAs have an inhibitory effect on the regulation of autophagy. It has been reported that miR-31 plays an important role in the development of colorectal cancer. However, what role miR-31 plays in colorectal cancer-associated fibroblasts (CAFs) has not been determined. In this study, we confirmed that the expression of miR-31 in CAFs was higher than in normal colorectal fibroblasts (NFs). We also found that treatment of CAFs with miR-31 mimic inhibited the expression of the autophagy-related genes Beclin-1, ATG, DRAM and LC3. In addition, we found up-regulation of miR-31 significantly affected colorectal cancer cell behaviors, including proliferation, invasion and apoptosis. Also, up-regulation of miR-31 in CAF could increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. In summary, miR-31 can inhibit autophagy in colorectal CAFs, affect colorectal cancer development, and increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. We hypothesize that miR-31 may become a new target of treatments for colorectal cancer.

Highlights

The tumor microenvironment is a tumor pathologyrelated environment that consists of tumor cells, stromal cells, cytokines, immune cells and other components
We found that miR-31 expression in cancer-associated fibroblasts (CAFs) was significantly lower than in normal colorectal fibroblasts (NFs) (Figure 3A)
MiRNAs in CAFs play an important role in the biological behavior of tumors

Summary

Introduction

The tumor microenvironment is a tumor pathologyrelated environment that consists of tumor cells, stromal cells, cytokines, immune cells and other components. This environment is characterized by tissue hypoxia, acidosis, and interstitial pressure. A large number of growth factors, proteolytic enzymes, and immune inflammatory response factors in the tumor microenvironment act jointly on the surface of tumor cells and have an important impact on cell proliferation, metastasis, and differentiation. CAFs provide nutritional support for the passive growth of the tumor, they promote the evolution of the tumor by regulating metabolism, immune responses, and the epithelial-mesenchymal transition. A variety of CAF-secreted active factors interact with epithelial cells, endothelial cells, pericytes and inflammatory cells to promote tumor evolution by regulating metabolism and immune responses. As a result of the above interactions, CAFs are becoming a new target for anti-cancer therapies. [1]

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Results

Conclusion