Long non-coding RNA PRR34-AS1 promotes hepatocellular carcinoma development via modulating Wnt/β-catenin pathway by absorbing miR-296-5p and up-regulating E2F2 and SOX12

Abstract Hepatocellular carcinoma (HCC) belongs to the most frequent cancer with high death rate worldwide. Thousands of long non-coding RNAs (lncRNAs) have been confirmed to influence the development of human cancers, including HCC. Nevertheless, the biological role of PRR34 antisense RNA 1 (PRR34-AS1) in HCC remains obscure. Here, we observed via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR) that PRR34-AS1 was highly expressed in HCC cells. Functional assays revealed that PRR34-AS1 promoted HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in vitro, and facilitated tumor growth in vivo. In addition, western blot analysis and TOP Flash/FOP Flash reporter assays verified that PRR34-AS1 stimulated Wnt/β-catenin pathway in HCC cells. Furthermore, RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays uncovered that PRR34-AS1 sequestered miR-296-5p to positively modulate E2F transcription factor 2 (E2F2) and SRY-box transcription factor 12 (SOX12) in HCC cells. Importantly, chromatin immunoprecipitation (ChIP) and luciferase reporter assays uncovered that E2F2 transcriptionally activated PRR34-AS1 in turn. Further, rescue experiments reflected that PRR34-AS1 affected HCC progression through targeting miR-296-5p/E2F2/SOX12/Wnt/β-catenin axis. Our findings found that PRR34-AS1 elicited oncogenic functions in HCC, which indicated that PRR34-AS1 might be a novel therapeutic target for HCC.