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miR-144-3p 通过靶向 GABRB2 抑制甲状腺癌细胞的体外进展。

miR-144-3p Targets GABRB2 to Suppress Thyroid Cancer Progression In Vitro.

机构信息

Department of Head and Neck Surgery, Hainan Cancer Hospital, Haikou, Hainan, 570000, P. R. China.

出版信息

Cell Biochem Biophys. 2024 Dec;82(4):3585-3595. doi: 10.1007/s12013-024-01446-y. Epub 2024 Aug 2.

Abstract

Thyroid cancer, as one of the most common cancers in many countries, has attracted increasing attention, but its pathogenesis is still unclear. This research explored the effects of miR-144-3p and GABRB2 on thyroid cancer cells and the underlying mechanism. Gene expression data was obtained from the GEO database to analyze differential expression of mRNAs and miRNAs in patients with thyroid cancer. CCK-8, transwell, scratch, and flow cytometry assays were performed to detect cell proliferation, invasion, migration, and apoptosis, respectively. Dual-luciferase reporters were used to detect the binding of miR-144-3p to GABRB2. GABRB2 was highly expressed and miR-144-3p was underexpressed in thyroid cancer. In thyroid cancer cells, inhibiting GABRB2 or upregulating miR-144-3p reduced proliferation, invasion, and migration and increased apoptotic rates; GABRB2 overexpression or miR-144-3p inhibition brought about the opposite results. miR-144-3p targeted GABRB2 and negatively regulated its expression. PI3K/AKT activation was reduced in thyroid cancer cells overexpressing miR-144-3p. GABRB2 overexpression partially mitigated the tumor-suppressive effect of miR-144-3p overexpression. In conclusion, miR-144-3p targets GABRB2 to inhibit PI3K/AKT activation, thereby inhibiting the progression of thyroid cancer in vitro.

摘要

甲状腺癌作为许多国家最常见的癌症之一,受到了越来越多的关注,但它的发病机制仍不清楚。本研究探讨了 miR-144-3p 和 GABRB2 对甲状腺癌细胞的影响及其潜在机制。从 GEO 数据库中获取基因表达数据,分析甲状腺癌患者中 mRNAs 和 miRNAs 的差异表达。通过 CCK-8、Transwell、划痕和流式细胞术实验分别检测细胞增殖、侵袭、迁移和凋亡。双荧光素酶报告实验检测 miR-144-3p 与 GABRB2 的结合。在甲状腺癌中,GABRB2 高表达,miR-144-3p 低表达。在甲状腺癌细胞中,抑制 GABRB2 或上调 miR-144-3p 可降低增殖、侵袭和迁移能力,增加凋亡率;过表达 GABRB2 或抑制 miR-144-3p 则产生相反的结果。miR-144-3p 靶向 GABRB2 并负调控其表达。在过表达 miR-144-3p 的甲状腺癌细胞中,PI3K/AKT 激活减少。GABRB2 的过表达部分缓解了 miR-144-3p 过表达的肿瘤抑制作用。综上所述,miR-144-3p 靶向 GABRB2 抑制 PI3K/AKT 激活,从而抑制甲状腺癌细胞在体外的进展。

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