The effects of UPF1 on lncRNA-HEIH stability in hepatocellular carcinoma

Abstract

It has been revealed that long non-coding RNAs (lncRNAs) play a critical role in hepatocellular carcinoma (HCC). The Long Non-Coding RNA High Expression In Hepatocellular Carcinoma (lncRNA-HEIH) facilitates tumor growth through interaction with enhancer of zeste homolog 2 (EZH2) in HCC. Although the functions of lncRNA-HEIH have been studied, the regulation mechanism of lncRNA-HEIH is not elucidated. RNA binding proteins (RBPs) are critical to the post-transcriptional regulation of RNA. One of the best-known RBPs is up-frameshift protein 1 (UPF1), a member of the superfamily 1 (SF1) RNA helicase. The different effects of UPF1 and lncRNA-HEIH in HCC have been identified, i.e., the overexpression of UPF1 and lncRNA-HEIH drives HCC growth in the opposite direction. Using transcriptome-wide analysis upon depletion of UPF1, we found that the expression of lncRNA-HEIH was regulated by UPF1, and the expression of lncRNA-HEIH was reversely correlated with the expression of UPF1. In addition, by analyzing public UPF1 cross-linking immunoprecipitation and sequencing (CLIP-seq), RNA immunoprecipitation (RIP), and mutagenesis experiments, we confirmed that UPF1 bound to lncRNA-HEIH. Our results suggest that UPF1 regulates the stability of lncRNA-HEIH by binding it.