UPF1 inhibits the hepatocellular carcinoma progression by targeting long non-coding RNA UCA1

Yongli Zhou,Yandong Li,Liqiao Ge,Na Wang,Jianyun Zheng,Xiuying Li

doi:10.1038/s41598-019-43148-z

Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. However, the molecular mechanism underlying HCC carcinogenesis remains to be further elucidated. Up-frameshift protein 1 (UPF1) is a RNA/DNA-dependent ATPase and ATP-dependent RNA helicase. Here, we explored the expression and function of UPF1 in HCC. In this study, we demonstrated that UPF1 expression was significantly reduced in hepatocellular carcinoma (HCC) tissues compared with the adjacent normal tissues. And further functional assays revealed that knockdown of UPF1 promoted HCC cells growth and invasion. Furthermore, we found that UPF1 could bind to long non-coding RNA urothelial cancer associated 1 (UCA1) and was negatively correlated with UCA1. UCA1 expression also affected HCC growth and invasion. Knockdown of UCA1 ameliorated the effect of UPF1 knock down on HCC growth and invasion. Knockdown of UPF1 enhances glycolysis in HCC. Taken together, our results provided new insights for finding novel therapeutic targets for hepatocellular carcinoma progression.

Highlights

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide[1]
We demonstrated that Up-frameshift protein 1 (UPF1) expression was significantly reduced in hepatocellular carcinoma (HCC) tissues compared with the adjacent normal tissues
IHC and real time PCR showed that UPF1 expression was decreased in HCC and might play an important role in tumor progression

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide[1]. UPF1 play a key player in nonsense mediated mRNA decay (NMD) and non-NMD RNA degradation[10]. UPF1 promotes cell progression through G1/S raising the possibility that NMD promotes the decay of mRNAs encoding inhibitory proteins that block progression through this stage of the cell cycle[11]. Recent study found that the human RNA surveillance factor UPF1 regulates tumorigenesis[12]. We demonstrated that UPF1 expression was significantly reduced in hepatocellular carcinoma (HCC) tissues compared with the adjacent normal tissues. Further functional assays revealed that knockdown of UPF1 promoted HCC cells growth and invasion. UCA1 expression affected HCC growth and invasion. Knockdown of UCA1 ameliorated the effect of UPF1 knock down on HCC growth and invasion. Our results provided new insights for finding novel therapeutic targets for hepatocellular carcinoma progression

Methods

Results

Conclusion