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微小RNA-1972通过靶向细胞周期中GZMH介导的DNA复制来抑制肝细胞癌的增殖。

miR-1972 inhibits hepatocellular carcinoma proliferation by targeting GZMH-mediated DNA replication in the cell cycle.

作者信息

Jin Yun, Dai Yihe, Qiao Ou, Hu Pingping, Han Jiang

机构信息

Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province Kunming, No. 157, Jinbi Road, Xishan District, Kunming, Yunnan 650032, China.

The Affiliated Hospital of Kunming University of Science and Technology, Kunming, No. 727, Jingming South Road, Chenggong District, Kunming, Yunnan, 650032, China.

出版信息

J Pharm Pharmacol. 2025 Jan 6;77(1):142-152. doi: 10.1093/jpp/rgae037.

Abstract

AIM

To understand the regulatory roles of miR-1972 and GZMH in hepatocellular carcinoma (HCC) and explore their potential as therapeutic biomarkers.

METHODS

In vitro verification of the regulation of malignant cell behavior by differential expression of miR-1972 in HCC cells. The GSE113996 dataset was studied using weighted gene co-expression network analysis (WGCNA) and differential expressed genes respectively to identify the key prognostic gene GZMH and assess the effect of its differential expression on the prognosis of the patient. Finally, the regulation of GZMH expression by miR-1972 was verified, and the effect of their combination on HCC cell behavior was analyzed.

RESULTS

Inhibition of miR-1972 can reduce cell proliferation, migration, and invasion, while overexpression of miR-1972 has the opposite effect in HCC cells. According to the data, a positive prognosis for HCC was linked with higher GZMH expression. Interestingly, miR-1972 was observed to reverse-regulate the expression of GZMH. Besides, the combined regulation of GZMH and miR-1972 has been discovered to affect the cell growth, invasive capacity, and migratory potential of HCC cells, especially the cell cycle arrest in the G2 phase.

CONCLUSIONS

miR-1972 regulates the malignant behavior of HCC cells, especially cell proliferation, by regulating GZMH expression.

摘要

目的

了解miR - 1972和GZMH在肝细胞癌(HCC)中的调控作用,并探索它们作为治疗生物标志物的潜力。

方法

在体外验证HCC细胞中miR - 1972差异表达对恶性细胞行为的调控。分别使用加权基因共表达网络分析(WGCNA)和差异表达基因研究GSE113996数据集,以鉴定关键预后基因GZMH,并评估其差异表达对患者预后的影响。最后,验证miR - 1972对GZMH表达的调控,并分析它们联合作用对HCC细胞行为的影响。

结果

抑制miR - 1972可降低细胞增殖、迁移和侵袭能力,而在HCC细胞中过表达miR - 1972则有相反作用。根据数据,HCC预后良好与较高的GZMH表达相关。有趣的是,观察到miR - 1972可反向调节GZMH的表达。此外,已发现GZMH和miR - 1972的联合调控会影响HCC细胞的生长、侵袭能力和迁移潜力,尤其是使细胞周期停滞在G2期。

结论

miR - 1972通过调控GZMH表达来调节HCC细胞的恶性行为,尤其是细胞增殖。

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