lncRNA PRR34-AS1 promotes HCC development via modulating Wnt/β-catenin pathway by absorbing miR-296-5p and upregulating E2F2 and SOX12

Autor: Minzhen Qin, Yiliang Meng, Chunying Luo, Shougao He, Fengxue Qin, Yixia Yin, Junling Huang, Hailiang Zhao, Jing Hu, Zhihua Deng, Yiying Qiu, Gaoyu Hu, Hanhe Pan, Zongshuai Qin, Zansong Huang, Tingzhuang Yi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Therapy: Nucleic Acids, Vol 25, Iss , Pp 37-52 (2021)
Druh dokumentu: article
ISSN: 2162-2531
DOI: 10.1016/j.omtn.2021.04.016
Popis: Hepatocellular carcinoma (HCC) belongs to the most frequent cancer with a 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 real-time reverse transcriptase polymerase chain reaction (quantitative real-time RT-PCR) 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 microRNA-296-5p (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.
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