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LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4

Gene Therapy volume 27, pages 495–504 (2020)Cite this article

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Abstract

Long noncoding RNA OIP5-AS1 has been observed to be increased in several cancers, however, its role and biological mechanism was poorly understood in HCC. Currently, we found OIP5-AS1 expression was upregulated in HCC cells compared with normal human liver cells. Knockdown of OIP5-AS1 suppressed HCC cell proliferation, induced cells cycle arrest and cells apoptosis. In addition, HCC cell migration and invasion capacity in vitro were also inhibited by OIP5-AS1 inhibition. Bioinformatics analysis revealed OIP5-AS1 could interact with miR-363-3p, thereby repressing HCC development. We also observed miR-363-3p was significantly decreased in HCC cells and overexpression of miR-363-3p repressed HCC progression. The correlation between OIP5-AS1 and miR-363-3p was confirmed by performing RIP assay and RNA pull-down assay. Subsequently, SOX4 was predicted as a target of miR-363-3p and miR-363-3p modulated SOX4 levels negatively in vitro. Apart from these, in vivo experiments established that OIP5-AS1 can suppress HCC development through regulating miR-363-3p and SOX4. Collectively, these demonstrated that OIP5-AS1 was involved in HCC progression via targeting miR-363-3p and SOX4. OIP5-AS1 can act as a novel candidate for HCC diagnosis, prognosis, and therapy.

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Fig. 1: The loss of OIP5-AS1 knockdown repressed HCC cell proliferation.
Fig. 2: Inhibition of OIP5-AS1 blocked the cell progression.
Fig. 3: OIP5-AS1-sponged miR-363-3p and SOX4 was a target for miR-363-3p in vitro.
Fig. 4: Downregulation of OIP5-AS1 suppressed HCC progression by regulating miR-363-3p and SOX4 in vivo.

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Data availability

The datasets used in this study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Guangxi Clinic Medicine Research Center of Hepatobiliary Diseases [grant numbers AD17129025], and the Guangxi Medical High-level Leading Talents Training “139” Project, Special Funding for Guangxi Special Experts.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Road, Baise, 533000, Guangxi Zhuang Autonomous Region, China

    Jianchu Wang, Qianli Tang, Libai Lu, Zongjiang Luo, Wenchuan Li, Yuan Lu & Jian Pu

  2. Clinic Medicine Research Center of Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Road, Baise, 533000, Guangxi Zhuang Autonomous Region, China

    Qianli Tang

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Contributions

JP and JW designed the study and the experiments. QT, LL, ZL, WL and YL performed the experiments. QT and LL collected the data and did the analysis. JW drafted the paper. JP revised the paper. All of the authors finally approved the proof for submission.

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Correspondence to Jian Pu.

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Wang, J., Tang, Q., Lu, L. et al. LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4. Gene Ther 27, 495–504 (2020). https://doi.org/10.1038/s41434-020-0123-2

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