LncRNA RP11-307C12.11 promotes the growth of hepatocellular carcinoma by acting as a molecular sponge of miR-138

Abstract

Background: Abnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all tumors in humans, providing numerous potential diagnostic and prognostic biomarkers, and therapeutic targets. Materials and methods: The Cancer Genome Atlas (TCGA) database was used to screen potential LncRNAs, and 30 paired hepatocellular carcinoma (HCC) tissues were used to investigate RP11-307C12.11 expression levels by qRT-PCR and another 105 HCC tissues by in situ hybridizsation (ISH). RP11-307C12.11 overexpression and knockdown experiments were performed to investigate the effects of RP11-307C12.11 on HCC growth through in vitro and in vivo assays (MTT assay, colony formation assay, EdU assay, and xenograft model). The molecular mechanism underlying these effects was confirmed by MS2-RIP-assay, RIP assay, luciferase assay, and rescue experiments. Results: RP11-307C12.11 expression level was significantly higher in tumor tissues than in the adjacent normal tissues. Elevated RP11-307C12.11 expression level was associated with poor prognosis of HCC patients, and it may be represented as an independent prognostic biomarker in patients with HCC. Functionally, RP11-307C12.11 overexpression promoted HCC growth both in vitro and in vivo; however, its knockdown reversed these effects. Mechanistically, we found that RP11-307C12.11 expressed predominantly in the cytoplasm and sponged microRNA (miR)-138 to regulate its common target CCND1 and PDK1. Conclusions: Thus, we found that RP11-307C12.11 acts as an oncogene in HCC by binding to miR-138, which might provide a novel target for HCC therapy. Keywords: Long non-coding RNAs (lncRNAs), LncRNA RP11-307C12.11, Hepatocellular carcinoma (HCC), Growth, MicroRNA (MiR)-138