Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
Biochem Biophys Res Commun. 2019 Jan 22;508(4):1133-1138. doi: 10.1016/j.bbrc.2018.12.060. Epub 2018 Dec 13.
Tripartite motif family-like 2 (TRIML2), a member of the TRIM proteins family, is closely related to Alzheimer's disease, however, no studies of TRIML2 have been published in the cancer research literature. In the current study, we investigated the expression level of TRIML2 and its molecular mechanisms in human oral squamous cell carcinoma (OSCC); reverse transcriptase-quantitative polymerase chain reaction, immunoblot analysis, and immunohistochemistry showed that TRIML2 is up-regulated significantly in OSCCs in vitro and in vivo. TRIML2 knockdown OSCC cells showed decreased cellular proliferation by cell-cycle arrest at G1 phase that resulted from down-regulation of CDK4, CDK6, and cyclin D1 and up-regulation of p21 and p27. Surprisingly, resveratrol, a polyphenol, led to not only down-regulation of TRIML2 but also cell-cycle arrest at G1 phase similar to TRIML2 knockdown experiments. Taken together, we concluded that TRIML2 might play a significant role in tumoral growth and that resveratrol may be a new drug for treating OSCC by interfering with TRIML2 function.
三结构域家族样蛋白 2(TRIML2)是 TRIM 蛋白家族的一员,与阿尔茨海默病密切相关,然而,癌症研究文献中尚未有关于 TRIML2 的研究。在本研究中,我们研究了 TRIML2 在人口腔鳞状细胞癌(OSCC)中的表达水平及其分子机制;逆转录定量聚合酶链反应、免疫印迹分析和免疫组织化学显示,TRIML2 在体外和体内的 OSCC 中显著上调。TRIML2 敲低 OSCC 细胞通过下调 CDK4、CDK6 和细胞周期蛋白 D1 以及上调 p21 和 p27 导致 G1 期细胞周期停滞,从而导致细胞增殖减少。令人惊讶的是,白藜芦醇,一种多酚,不仅导致 TRIML2 的下调,而且还导致类似于 TRIML2 敲低实验的 G1 期细胞周期停滞。综上所述,我们得出结论,TRIML2 可能在肿瘤生长中发挥重要作用,白藜芦醇可能通过干扰 TRIML2 功能成为治疗 OSCC 的新药。