Ouyang Ying, Jiang Fangfang, Zeng Binghui, Wei Changbo, Yu Dongsheng
Guangdong Provincial Key Laboratory of Stomatology, Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University Guangzhou 510055, Guangdong, P.R. China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11251-11259. eCollection 2017.
Tumor metastasis is the main cause of death in patients with oral squamous cell carcinoma (OSCC). Epithelial-to-mesenchymal transition (EMT) is potentially associated with metastasis and histological grading in OSCC. Therefore, the discovery of new strategies to inhibit EMT is potentially valuable for the development of therapies for OSCC. In our previous study, we found that miR-222, which is up-regulated in OSCC, regulates the biological behavior of OSCC cells by targeting the p53-upregulated modulator of apoptosis (PUMA); however, the effect of miR-222 on TGF-β1-induced EMT in OSCC cells is unclear. In this study, OSCC cell lines CAL-27 and Tca-8113 were incubated with 5 ng/ml of TGF-β1 to inhibit the expression of E-cadherin, promote the expression of N-cadherin, vimentin, and α-SMA and stimulate achange in cell shape convert from a "cuboidal" epithelial structure into an elongated mesenchymal shape. We found that the expression of miR-222 was up-regulated during TGF-β1-induced EMT in OSCC cells. In addition, miR-222 knockdown reversed TGF-β1-induced EMT by targeting PUMA. Our findings indicate that miR-222 plays an important role in OSCC, potentially serving as a novel therapeutic target for the treatment of OSCC.
肿瘤转移是口腔鳞状细胞癌（OSCC）患者死亡的主要原因。上皮-间质转化（EMT）可能与OSCC的转移和组织学分级有关。因此，发现抑制EMT的新策略对OSCC治疗的发展可能具有重要价值。在我们之前的研究中，我们发现miR-222在OSCC中上调，通过靶向p53上调的凋亡调节因子（PUMA）来调节OSCC细胞的生物学行为；然而，miR-222对TGF-β1诱导的OSCC细胞EMT的影响尚不清楚。在本研究中，将OSCC细胞系CAL-27和Tca-8113与5 ng/ml的TGF-β1孵育，以抑制E-钙黏蛋白的表达，促进N-钙黏蛋白、波形蛋白和α-平滑肌肌动蛋白的表达，并刺激细胞形状从“立方形”上皮结构转变为细长的间充质形状。我们发现，在TGF-β1诱导的OSCC细胞EMT过程中，miR-222的表达上调。此外，miR-222敲低通过靶向PUMA逆转了TGF-β1诱导的EMT。我们的研究结果表明，miR-222在OSCC中起重要作用，可能成为治疗OSCC的新治疗靶点。
