1,4,5,6,7,8‑Hexahydropyrido[4,3‑d]pyrimidine inhibits HepG2 cell proliferation, migration and invasion, and induces apoptosis through the upregulation of miR‑26b‑5p by targeting CDK8

Luo,Hanlin; Yang,Yang; Zhou,Yanqiu; Bai,Xianyong; Hou,Yun

doi:10.3892/ol.2023.13846

1,4,5,6,7,8‑Hexahydropyrido[4,3‑d]pyrimidine inhibits HepG2 cell proliferation, migration and invasion, and induces apoptosis through the upregulation of miR‑26b‑5p by targeting CDK8

Authors:
- Hanlin Luo
- Yang Yang
- Yanqiu Zhou
- Xianyong Bai
- Yun Hou
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Affiliations: Department of Histology and Embryology, College of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: May 2, 2023 https://doi.org/10.3892/ol.2023.13846
Article Number: 260
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

1,4,5,6,7,8‑Hexahydropyrido[4,3‑d]pyrimidine (PPM) promotes apoptosis of HepG2 cells and serves a role in tumor suppression. However, the role of microRNA (miRNA) regulation in initiating apoptosis remains unclear. Therefore, the present study performed reverse transcription‑quantitative PCR to investigate the association between PPM and miRNA, which demonstrated that PPM upregulated the expression of miR‑26b‑5p. Wound healing and Transwell assays showed that PPM inhibited the migration and invasion of HepG2 cells, and EdU staining experiments showed that PPM inhibited the proliferation of HepG2 cells. Transfection with miR‑26b‑5p inhibitor reversed the effects of PPM on HepG2 cells. Flow cytometry results showed that PPM promoted apoptosis of HepG2 cells by upregulating miRNA (miR)‑26b‑5p, and Western blotting results showed that PPM promoted the expression of apoptosis‑associated protein Bax and inhibited the expression of Bcl‑2 by upregulating miR‑26b‑5p. Using a proteomic approach combined with bioinformatics analysis, CDK8 was identified as a potential target of miR‑26b‑5p and was downregulated by miR‑26b‑5p overexpression. However, PPM induced HepG2 cell cycle arrest without the involvement of miR‑26b‑5p. Western blotting results showed that PPM upregulation of miR‑26b‑5p suppresses NF‑κB/p65 signaling pathway in HepG2 cells by targeting of CDK8. The present results suggested that miR‑26b‑5p may function as a target gene of PPM and may serve a role in hepatocellular carcinoma treatment.

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