Department of Stomatology, Linyi People's Hospital, 276000, Linyi, P. R. China.
Cancer Gene Ther. 2022 Jan;29(1):62-72. doi: 10.1038/s41417-020-00289-y. Epub 2021 Feb 2.
microRNAs (miRNAs) have been revealed to participate in some oral cancers and are proved to be effective. In the present study, we tried to explore the biological function of miR-133a in oral squamous cell carcinoma (OSCC) cells. The relationship that C-terminal-binding proteins 2 (CTBP2) was the putative target gene of miR-133a revealed from bioinformatics analysis was further was further validated by dual-luciferase reporter gene assay. In total, 40 patients with OSCC were enrolled for characterization of miR-133a, CTBP2, and Notch signaling pathway-related gene expression in clinical OSCC tissues. Low expression of miR-133a and high expression of CTBP2, Hes1, Notch-1, and Notch-3 were determined in OSCC tissues. OSCC cell lines were transfected with miR-133a inhibitor, miR-133a mimic, or shRNA targeting CTBP2, in response to which cell proliferation, migration, invasion, cell cycle, and apoptosis were evaluated. Transfection of miR-133a mimic induced apoptosis and inhibited OSCC cell proliferation, migration, and invasion and this was demonstrated to be attributable to decreased CTBP2 expression and suppression of the Notch signaling pathway. Taken together, we concluded that miR-133a acted as a tumor suppressor in OSCC through inhibition of the Notch signaling pathway via binding to CTBP2.
microRNAs (miRNAs) 已被证明参与了一些口腔癌的发生,并且具有有效性。在本研究中,我们试图探索 miR-133a 在口腔鳞状细胞癌 (OSCC) 细胞中的生物学功能。生物信息学分析显示,C 端结合蛋白 2 (CTBP2) 是 miR-133a 的假定靶基因,双荧光素酶报告基因实验进一步验证了这一关系。总共招募了 40 名 OSCC 患者,用于在临床 OSCC 组织中对 miR-133a、CTBP2 和 Notch 信号通路相关基因的表达进行特征描述。在 OSCC 组织中,miR-133a 的表达较低,CTBP2、Hes1、Notch-1 和 Notch-3 的表达较高。用 miR-133a 抑制剂、miR-133a 模拟物或靶向 CTBP2 的 shRNA 转染 OSCC 细胞系,评估细胞增殖、迁移、侵袭、细胞周期和凋亡。转染 miR-133a 模拟物诱导了细胞凋亡,抑制了 OSCC 细胞的增殖、迁移和侵袭,这归因于 CTBP2 表达的降低和 Notch 信号通路的抑制。总之,我们得出结论,miR-133a 通过与 CTBP2 结合抑制 Notch 信号通路,在 OSCC 中发挥肿瘤抑制作用。