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miR-597-5p 通过靶向转录增强子关联域转录因子 1(TEAD1)抑制肝细胞癌的进展。

MiR-597-5p suppresses the progression of hepatocellular carcinoma via targeting transcriptional enhancer associate domain transcription factor 1 (TEAD1).

机构信息

The Second Department of General Surgery, Jincheng People's Hospital, 456 Wenchang East Street, Jincheng, 048026, Shanxi, China.

出版信息

In Vitro Cell Dev Biol Anim. 2022 Feb;58(2):96-108. doi: 10.1007/s11626-021-00614-1. Epub 2022 Feb 15.

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high incidence and mortality. MiR-597-5p is downregulated in tumor tissues of HCC compared with non-tumor tissues. However, its role in HCC is still unknown. This study aims to assess the function of miR-597-5p in HCC development and investigate the underlying mechanism. To perform gain- and loss-of-function studies, SK-HEP-1 cells and Huh-7 cells were transfected with miR-597-5p mimics and inhibitor, respectively. MiR-597-5p markedly reduced the cell viability and the expression of Ki-67 in HCC cells. MiR-597-5p also repressed the cell cycle progression of HCC cells and the protein levels of cyclin D1 and CDK2. Moreover, miR597-5p inhibited the migration and invasion of HCC cells and decreased MMP2 and MMP9 levels. Transcriptional enhancer associate domain transcription factor 1 (TEAD1) was identified as a target of miR-597-5p by luciferase reporter assay. TEAD1 and its downstream target genes, CTGF and CYR61, were downregulated by miR-597-5p in HCC cells. Furthermore, miR-597-5p was demonstrated to function in HCC progression by targeting TEAD1 via TEAD1 expression gain and loss. Our study demonstrates that miR-597-5p represses the proliferation, migration, and invasion of HCC cells through targeting TEAD1, which provides a therapeutic target for HCC treatment.

摘要

肝细胞癌(HCC)是最常见的原发性肝癌,发病率和死亡率都很高。与非肿瘤组织相比,miR-597-5p 在肿瘤组织中下调。然而,其在 HCC 中的作用尚不清楚。本研究旨在评估 miR-597-5p 在 HCC 发展中的作用,并探讨其潜在机制。为了进行增益和缺失功能研究,分别用 miR-597-5p 模拟物和抑制剂转染 SK-HEP-1 细胞和 Huh-7 细胞。miR-597-5p 显著降低了 HCC 细胞的细胞活力和 Ki-67 的表达。miR-597-5p 还抑制了 HCC 细胞的细胞周期进程,下调了细胞周期蛋白 D1 和 CDK2 的蛋白水平。此外,miR597-5p 抑制了 HCC 细胞的迁移和侵袭,并降低了 MMP2 和 MMP9 的水平。转录增强子相关结构域转录因子 1(TEAD1)通过荧光素酶报告基因检测被鉴定为 miR-597-5p 的靶标。miR-597-5p 在 HCC 细胞中下调 TEAD1 及其下游靶基因 CTGF 和 CYR61。此外,通过 TEAD1 表达增益和缺失证实 miR-597-5p 通过靶向 TEAD1 在 HCC 进展中发挥作用。我们的研究表明,miR-597-5p 通过靶向 TEAD1 抑制 HCC 细胞的增殖、迁移和侵袭,为 HCC 的治疗提供了一个治疗靶点。

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