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miR-99a-5p 通过靶向 CDC25A/IL6 抑制宫颈鳞癌细胞上皮间质转化

MiR-99a-5p Constrains Epithelial-Mesenchymal Transition of Cervical Squamous Cell Carcinoma Via Targeting CDC25A/IL6.

机构信息

Department of Obstetrics and Gynecology, Wuxi No. 2 Chinese Medicine Hospital, 390 Xincheng Road, Binhu District, Wuxi City, 214026, Jiangsu Province, China.

出版信息

Mol Biotechnol. 2022 Nov;64(11):1234-1243. doi: 10.1007/s12033-022-00496-y. Epub 2022 May 9.

Abstract

MiR-99a-5p participates in processes and pathogenesis of varying diseases. However, the molecular mechanism of miR-99a-5p in human cervical squamous cell carcinoma (CSCC) remains unclear. Here, we found that miR-99a-5p was lowly expressed in CSCC cells and negatively associated with overall survival. In addition, cellular experiments including CCK8, wound healing, Transwell and flow cytometry assays disclosed that transfection of miR-99a-5p mimic could suppress the cell activity, cell migratory, and invasive abilities, and promote cell apoptosis, thus inhibiting the tumor progression of CSCC cells. Luciferase reporter gene assay indicated that miR-99a-5p targeted 3'-UTR of CDC25A. Also, enforced CDC25A level rescued the impact of miR-99a-5p on CSCC progression. Silencing CDC25A could restrain the mRNA and protein levels of IL-6 in CSCC. CDC25A overexpression or IL-6 treatment could attenuate inhibiting impact of miR-99a-5p overexpression on epithelial-mesenchymal transition (EMT). These findings suggested that miR-99a-5p may play an anti-tumor role in tumor metastasis by targeting CDC25A/IL6 to hamper EMT process, which revealed a novel molecular mechanism in CSCC.

摘要

miR-99a-5p 参与多种疾病的发生发展过程,但 miR-99a-5p 在人宫颈鳞癌(CSCC)中的分子机制尚不清楚。本研究发现 miR-99a-5p 在 CSCC 细胞中低表达,与总生存期呈负相关。此外,包括 CCK8、划痕愈合、Transwell 和流式细胞术在内的细胞实验表明,转染 miR-99a-5p 模拟物可抑制细胞活性、细胞迁移和侵袭能力,并促进细胞凋亡,从而抑制 CSCC 细胞的肿瘤进展。荧光素酶报告基因实验表明,miR-99a-5p 靶向 CDC25A 的 3'-UTR。此外,增强 CDC25A 水平可挽救 miR-99a-5p 对 CSCC 进展的影响。沉默 CDC25A 可抑制 CSCC 中 IL-6 的 mRNA 和蛋白水平。CDC25A 过表达或 IL-6 处理可减弱 miR-99a-5p 过表达对上皮间质转化(EMT)的抑制作用。这些发现表明,miR-99a-5p 通过靶向 CDC25A/IL6 抑制 EMT 过程在肿瘤转移中发挥抑瘤作用,揭示了 CSCC 中的一个新的分子机制。

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