GRHPR, Targeted by miR-138-5p, Inhibits the Proliferation and Metastasis of Hepatocellular Carcinoma Through PI3K/AKT Signaling Pathway
Publication: Cancer Biotherapy & Radiopharmaceuticals
Volume 39, Issue Number 10
Abstract
Background: Hepatocellular carcinoma (HCC) is a highly aggressive cancer. This study elucidates the role of Glyoxylate reductase/hydroxypyruvate reductase (GRHPR) in HCC proliferation and metastasis, along with its molecular mechanism, and identifies miRNAs targeting GRHPR.
Materials and Methods: Expression levels of GRHPR and miR-138-5p were assessed using real-time fluorescent quantitative polymerase chain reaction and Western blot techniques. Bioinformatic analysis was employed to identify miRNAs targeting GRHPR, and the results were confirmed via dual-luciferase reporter assays. HCC cell lines overexpressing GRHPR were established to investigate its roles in cell proliferation, migration, and invasion. The biological function of miR-138-5p targeting GRHPR in HCC cells was also evaluated. Furthermore, a xenograft mouse model was utilized to examine the in vivo functions of GRHPR.
Results: GRHPR expression was downregulated in HCC, whereas miR-138-5p was upregulated. Overexpression of GRHPR suppressed HCC cell proliferation, migration, and invasion. Conversely, inhibition of GRHPR by miR-138-5p promoted HCC cell proliferation and invasive properties. MiR-138-5p was found to regulate Phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) phosphorylation levels by inhibiting GRHPR expression.
Conclusion: This study highlights GRHPR’s role as a tumor suppressor in HCC, with its function being regulated by miR-138-5p.
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Information & Authors
Information
Published In
Cancer Biotherapy & Radiopharmaceuticals
Volume 39 • Issue Number 10 • December 2024
Pages: 733 - 744
PubMed: 38934120
Copyright
Copyright 2024, Mary Ann Liebert, Inc., publishers.
History
Published online: 4 December 2024
Published in print: December 2024
Published ahead of print: 27 June 2024
Authors
Authors’ Contributions
J.Z., Y.L., and Q.Z. conceptualized the study. S.Y., B.Z., and J.L. conducted the experiments. F.X., M.Y., and Y.C. performed data analysis. C.L., T.L., and Y.Z. contributed to figure preparation. S.Y. and Y.L. drafted the article.
Disclosure Statement
The authors declare no competing interest.
Funding Information
This research was supported by the Key Scientific and Technological Project of Henan Province (Grant No. 222102310083, No. 222102310252) and the Project of Basic Research Fund of Henan Institute of Medical and Pharmacological Sciences (Grant No. 2022BP0103, No. 2022BP0118).
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