U1RNP/lncRNA/Transcription Cycle Axis Promotes Tumorigenesis of Hepatocellular Carcinoma

Abstract

As a component of the spliceosome, U1 small nuclear ribonucleoproteins (U1RNPs) play critical roles in RNA splicing, and recent studies have shown that U1RNPs could recruit long non-coding RNAs (lncRNAs) to chromatin which are involved in cancer development. However, the interplay of U1 snRNP, lncRNAs and downstream genes and signaling pathways are insufficiently understood in hepatocellular carcinoma (HCC). The expression of U1RNPs was found to be significantly higher in tumors than normal tissues in liver hepatocellular carcinomas of The Cancer Genome Atlas (TCGA-LIHC) dataset. LncRNAs with potential U1-binding sites (termed U1-lncRNAs) were found to be mostly located in the nucleus and their expression was higher in tumor than in normal tissues Bioinformatic analysis indicated that U1-lncRNAs worked with RNA-binding proteins and regulated the transcription cycle in HCC. A U1-lncRNA risk model was constructed using a TCGA dataset, and the AUCs of this risk model to predict 1-, 3- and 5-year overall survival were 0.82, 0.84 and 0.8, respectively. Furthermore, silencing of the small nuclear ribonucleoprotein D2 polypeptide (SNRPD2) resulted in impaired proliferation, G1/M cell cycle arrest and downregulation of transcription-cycle-related genes in HCC cell lines. Taken together, these results indicate that U1RNPs interact with lncRNAs and promote the transcription cycle process in HCC, which suggests that these could be novel biomarkers in the clinical management of HCC.