Chi Hongyu
Department of Stomatology, Daqing Oilfield General Hospital, Daqing, Heilongjing Province, People's Republic of China.
Biomed Pharmacother. 2015 Apr;71:53-7. doi: 10.1016/j.biopha.2015.02.011. Epub 2015 Feb 26.
Growing evidence supports that microRNAs (miRNAs) play crucial roles in cancer progression by directly downregulating multiple targets. However, the underlying mechanisms of miRNAs in oral squamous cell carcinoma (OSCC) are poorly understood. In the current study, we found that miR-194 expression was markedly downregulated in both clinical OSCC tissues and OSCC cell lines, compared with adjacent non-cancerous tissues and normal tongue epithelial cell TEC, respectively. Overexpression of miR-194 suppressed, whereas miR-194-in promoted OSCC cell proliferation. Furthermore, we demonstrated that miR-194 could reduce the phosphoinositide 3-kinase (PI3K)/AKT/FoxO3a signaling pathway by suppressing acylglycerol kinase (AGK) directly, resulting in decreasing cyclin D1 expression and increasing expression of p21 in OSCC. In sum, our data provide compelling evidence that miR-194 functions as a potential tumor suppressor by inhibiting the PI3K/AKT/FoxO3a signaling pathway and might sever as a potential therapeutic target for OSCC patients.
越来越多的证据支持微小RNA(miRNA)通过直接下调多个靶点在癌症进展中发挥关键作用。然而,miRNA在口腔鳞状细胞癌(OSCC)中的潜在机制仍知之甚少。在本研究中,我们发现与相邻的非癌组织和正常舌上皮细胞TEC相比,miR-194在临床OSCC组织和OSCC细胞系中的表达均显著下调。miR-194的过表达抑制了OSCC细胞增殖,而miR-194抑制则促进了OSCC细胞增殖。此外,我们证明miR-194可通过直接抑制酰基甘油激酶(AGK)来降低磷酸肌醇3激酶(PI3K)/AKT/FoxO3a信号通路,从而导致OSCC中细胞周期蛋白D1表达降低和p21表达增加。总之,我们的数据提供了令人信服的证据,表明miR-194通过抑制PI3K/AKT/FoxO3a信号通路发挥潜在的肿瘤抑制作用,可能成为OSCC患者的潜在治疗靶点。