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Circ_0124208 Promotes the Progression of Hepatocellular Carcinoma by Regulating the miR-338-3p/LAMC1 Axis

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Abstract

Hundreds of circular RNAs (circRNAs) have been identified as key regulators in biological processes; however, only few of these circRNAs have been functionally described to participate in the development of hepatocellular carcinoma (HCC). The present study aimed to reveal the function and molecular mechanisms of circ_0124208 in HCC. Real-time quantitative PCR revealed the upregulation of circ_0124208 in HCC tissues and cells. Based on cell functional experiments, silencing circ_0124208 attenuated proliferation and migration, but boosted the apoptosis of Hep 3B and Huh7 cells in vitro. The in vivo experiment further validated the repression of tumor growth via circ_0124208 knockdown. RNA immunoprecipitation and dual-luciferase reporter assays showed that circ_0124208 sponged miR-338-3p and reduced its expression. miR-338-3p inhibition was found to partially reverse the tumor-suppressive effects caused by circ_0124208 in Hep 3B and Huh7 cells. Furthermore, miR-338-3p directly targeted laminin subunit gamma 1 (LAMC1). The malignancy of Hep 3B and Huh7 cell was decreased by LAMC1 knockdown, and this effect was mitigated by miR-338-3p suppression. Overall, circ_0124208 was demonstrated for the first time to play a crucial role as an oncogene in HCC, implying that it could be a useful biomarker for HCC diagnosis. Furthermore, the circ_0124208/miR-338-3p/LAMC1 axis can be used as a potential therapeutic target for HCC treatment.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Nanchong, 637000, Sichuan, China

    Jianyu Chen, Zhi Liu, Yang Zhong, Hui Chen & Liang Xie

  2. Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, No. 1 Maoyuan South Road, Nanchong, 637000, Sichuan, China

    Jianyu Chen, Zhi Liu, Yang Zhong, Hui Chen & Liang Xie

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Contributions

The research was created and is being led by JYC. ZL and YZ developed the approach and carried out the research. HC discover the needed resources. Analyzing the data and performing the tests were performed by LX. The paper was written by ZL and YZ. The manuscript was read and modified by JYC, HC, and LX. All authors have reviewed and approved the manuscript.

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Correspondence to Liang Xie.

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The Affiliated Hospital of North Sichuan Medical College's Ethics Committee gave its consent to the current study (Nanchong, China). The handling of clinical tissue samples complies with the values set out in the Declaration of Helsinki. Each patient signed an informed consent form in writing. The Affiliated Hospital of North Sichuan Medical College's Ethics Committee approved this animal experiment, which was carried out in compliance with the ARRIVE criteria.

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Chen, J., Liu, Z., Zhong, Y. et al. Circ_0124208 Promotes the Progression of Hepatocellular Carcinoma by Regulating the miR-338-3p/LAMC1 Axis. Mol Biotechnol 65, 1750–1763 (2023). https://doi.org/10.1007/s12033-023-00686-2

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