MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells.

Weibin Wang,Guotao Sun,Siqi Liu,Yu Yang,Xueju Wei,Yupei Zhao,Fang Wang,Junwu Zhang,Lijun Zhao,Yanni Ma,Jia Yu,Lanlan Wang

doi:10.1038/srep27641

Abstract

The drug-resistance of pancreatic cancer cells results in poor therapeutic effect. To predict the therapeutic effect of the chemotherapy drugs to specific patients and to reverse the resistance of pancreatic cancer cells are critical for chemotherapy of pancreatic cancer. MicroRNAs (miRNAs) have been reported to play important roles in the genesis of drug-resistance of various cancer types. There are also many advantages of miRNAs in diagnosis and therapy of disease. Although several miRNAs regulating 5-Fluorouracil (5-FU) resistance in human pancreatic cancer have been reported, the detailed molecular mechanism remains to be determined. In this study, we found that miR-320a was significantly up-regulated in 5-FU resistant pancreatic cancer cells. Over-expression of miR-320a strongly contributed to pathogenesis of pancreatic cancer, which was represented by the increased proliferation, invasion, metastasis, drug-resistance characteristics and the epithelial-to-mesenchymal transition. Furthermore, we demonstrated that miR-320a was able to bind to 3′UTR of PDCD4 mRNA, and mediated its down-regulation in 5-FU resistance of human pancreatic cancer cells. Whereas restoration of PDCD4 expression could partially attenuate the function of miR-320a in pancreatic cancer. Taken together, our study demonstrated that miR-320a played important role in regulating 5-FU resistance by targeting PDCD4 and might be developed as new therapeutic target for pancreatic cancer.

Highlights

The world has seen a booming of pancreatic cancer during the past years
Studies have shown that epithelial-mesenchymal transition (EMT), cancer stem cells and microRNAs play key roles in the formation of drug resistance during the pancreatic cancer chemotherapy[5,6,7]
We identify that miR-320a plays an important role in promoting 5-FU resistance of human pancreatic cancer cells by targeting Programmed cell death 4 (PDCD4), and facilitating several aspects of pancreatic cancer pathogenesis, including proliferation, invasion, metastasis, drug-resistance characteristics and the epithelial-to-mesenchymal transition

Summary

Introduction

The world has seen a booming of pancreatic cancer during the past years. The latest surveys suggest that the incidence of pancreatic cancer increased three times during the past 10 years[1], ranking the fourth disease of cancer mortality all over the world, which ranks the seventh in China[2,3]. Studies have shown that epithelial-mesenchymal transition (EMT), cancer stem cells and microRNAs (miRNAs) play key roles in the formation of drug resistance during the pancreatic cancer chemotherapy[5,6,7]. Emerging evidence implicates the critical role of miRNAs because they are key regulatory molecules in various biological and pathological processes including EMT. These small, noncoding molecules elicit their regulatory effects by imperfectly binding to the 3′untranslated region (3′UTR) of target mRNA, causing either degradation of mRNA or inhibition of their translation to functional proteins[10,11]. The expression of some drug resistance related miRNAs is closely correlative with the survival of patients with pancreatic cancer chemotherapy

Methods

Results

Conclusion