A novel long non-coding RNA RP11-286H15.1 represses hepatocellular carcinoma progression by promoting ubiquitination of PABPC4.

Abstract

Hepatocellular carcinoma (HCC) is a malignancy found at high frequency around the world. Unfortunately, the scarcity of effective early diagnostic methods invariably results in poor outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the progression of hepatocellular carcinoma (HCC). A novel lncRNA RP11-286H15.1(OTTHUMG00000186042) has been identified and associated with HCC; however, the potential role of RP11-286H15.1 in HCC remains undefined. The transcript abundance of RP11-286H15.1 in 80 pairs of HCC samples and cell lines was evaluated by qRT-PCR analysis. The functional role of RP11-286H15.1 in HCC was tested in vivo and in vitro. The mechanisms underlying the role of RP11-286H15.1 in HCC were explored by RNA pulldown, transcriptome sequencing, and RNA immunoprecipitation (RIP), ubiquitination and fluorescence in situ hybridization (FISH) assays as well as Western blot analysis. The qRT-PCR and FISH assays revealed that RP11-286H15.1 was significantly decreased in HCC, and implied a shorter survival time. RP11-286H15.1 overexpression inhibited HCC cell proliferation and metastasis in vitro and in vivo, whereas RP11-286H15.1 knockdown produced the opposite results. Furthermore, we confirmed that RP11-286H15.1 (620-750 nucleotides) binds to poly(A) binding protein 4 (PABPC4) and promotes its ubiquitination, thus, reducing the stability of TRIM37 and CDC27 mRNAs. Our study demonstrates that a novel lncRNA, RP11-286H15.1, represses HCC progression by promoting PABPC4 ubiquitination. These findings highlight potential therapeutic targets for HCC.