1,4,5,6,7,8-六氢吡啶并[4,3-d]嘧啶抑制 HepG2 细胞增殖、迁移和侵袭，并通过靶向 CDK8 上调 miR-26b-5p 诱导细胞凋亡。,Oncology Letters

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1,4,5,6,7,8-六氢吡啶并[4,3-d]嘧啶抑制 HepG2 细胞增殖、迁移和侵袭，并通过靶向 CDK8 上调 miR-26b-5p 诱导细胞凋亡。
Oncology Letters ( IF 2.5 ) Pub Date : 2023-05-02 , DOI: 10.3892/ol.2023.13846
Hanlin Luo ₁ , Yang Yang ₁ , Yanqiu Zhou ₁ , Xianyong Bai ₁ , Yun Hou ₁

Affiliation

1,4,5,6,7,8-Hexahydropyrido[4,3-d]pyrimidine (PPM) 促进 HepG2 细胞凋亡，并在肿瘤抑制中发挥作用。然而，microRNA (miRNA) 调节在启动细胞凋亡中的作用仍不清楚。因此，本研究进行了逆转录-定量 PCR 来研究 PPM 和 miRNA 之间的关联，这表明 PPM 上调了 miR-26b-5p 的表达。伤口愈合和Transwell实验表明PPM抑制了HepG2细胞的迁移和侵袭，EdU染色实验表明PPM抑制了HepG2细胞的增殖。用 miR-26b-5p 抑制剂转染可逆转 PPM 对 HepG2 细胞的影响。流式细胞术结果显示PPM通过上调miRNA（miR）-26b-5p促进HepG2细胞凋亡，Western blotting结果显示PPM通过上调miR-26b-5p促进凋亡相关蛋白Bax的表达，抑制Bcl-2的表达。使用蛋白质组学方法结合生物信息学分析，CDK8 被确定为 miR-26b-5p 的潜在靶标，并被 miR-26b-5p 过表达下调。然而，PPM 在没有 miR-26b-5p 参与的情况下诱导 HepG2 细胞周期停滞。Western blotting 结果显示，PPM 上调 miR-26b-5p 通过靶向 CDK8 抑制 HepG2 细胞中的 NF-κB/p65 信号通路。目前的结果表明，miR-26b-5p 可能作为 PPM 的靶基因发挥作用，并可能在肝细胞癌治疗中发挥作用。使用蛋白质组学方法结合生物信息学分析，CDK8 被确定为 miR-26b-5p 的潜在靶标，并被 miR-26b-5p 过表达下调。然而，PPM 在没有 miR-26b-5p 参与的情况下诱导 HepG2 细胞周期停滞。Western blotting 结果表明，PPM 上调 miR-26b-5p 通过靶向 CDK8 抑制 HepG2 细胞中的 NF-κB/p65 信号通路。目前的结果表明，miR-26b-5p 可能作为 PPM 的靶基因发挥作用，并可能在肝细胞癌治疗中发挥作用。使用蛋白质组学方法结合生物信息学分析，CDK8 被确定为 miR-26b-5p 的潜在靶标，并被 miR-26b-5p 过表达下调。然而，PPM 在没有 miR-26b-5p 参与的情况下诱导 HepG2 细胞周期停滞。Western blotting 结果显示，PPM 上调 miR-26b-5p 通过靶向 CDK8 抑制 HepG2 细胞中的 NF-κB/p65 信号通路。目前的结果表明，miR-26b-5p 可能作为 PPM 的靶基因发挥作用，并可能在肝细胞癌治疗中发挥作用。Western blotting 结果显示，PPM 上调 miR-26b-5p 通过靶向 CDK8 抑制 HepG2 细胞中的 NF-κB/p65 信号通路。目前的结果表明，miR-26b-5p 可能作为 PPM 的靶基因发挥作用，并可能在肝细胞癌治疗中发挥作用。Western blotting 结果显示，PPM 上调 miR-26b-5p 通过靶向 CDK8 抑制 HepG2 细胞中的 NF-κB/p65 信号通路。目前的结果表明，miR-26b-5p 可能作为 PPM 的靶基因发挥作用，并可能在肝细胞癌治疗中发挥作用。

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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.

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.

更新日期：2023-05-02

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