Department of Periodontology, Stomatology Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710004, P.R. China.
Department of Genetics and Molecular Biology, Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Int J Oncol. 2015 Oct;47(4):1528-36. doi: 10.3892/ijo.2015.3135. Epub 2015 Aug 27.
Dysregulation of microRNAs (miRNAs) has been associated with carcinogenesis in oral squamous cell carcinoma (OSCC). In the present study, we investigated the expression and function of miR-99b-3p in human OSCC. We found that the expression levels of miR-99b-3p decreased in 21 clinical OSCC samples (84%). Furthermore, ectopic expression of miR-99b-3p inhibited OSCC cell proliferation by downregulating glycogen synthase kinase-3β (GSK3β), an miR-99b-3p' target gene, at the mRNA and protein levels, both in vitro and in vivo. Moreover, the silencing of GSK3β recapitulated the cellular and molecular effects in a similar manner to the overexpression of miR-99b-3p, which included inhibition of OSCC cell proliferation and suppression of p65 (RelA) and G1 regulators (cyclin D1, CDK4 and CDK6) in vitro. Our data suggest that miR-99b-3p functions as a tumor suppressor in OSCC via GSK3β downregulation.
miRNAs 的失调与口腔鳞状细胞癌（OSCC）的发生有关。在本研究中，我们研究了 miR-99b-3p 在人 OSCC 中的表达和功能。我们发现 miR-99b-3p 的表达水平在 21 个临床 OSCC 样本中降低（84%）。此外，miR-99b-3p 的异位表达通过下调糖原合酶激酶-3β（GSK3β），即 miR-99b-3p 的靶基因，在体外和体内均抑制了 OSCC 细胞的增殖，在 mRNA 和蛋白水平上均如此。此外，GSK3β 的沉默以类似于 miR-99b-3p 过表达的方式再现了细胞和分子效应，包括抑制 OSCC 细胞增殖以及抑制 p65（RelA）和 G1 调节剂（细胞周期蛋白 D1、CDK4 和 CDK6）在体外。我们的数据表明，miR-99b-3p 通过下调 GSK3β 在 OSCC 中发挥肿瘤抑制作用。
