Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Gastrointestinal Surgery, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):91-99. doi: 10.1016/j.bbrc.2018.10.172. Epub 2018 Nov 2.
Numerous studies have shown that CMTM family members have a variety of important roles in the occurrence and progression of cancer. CMTM7 has also been reported to be down-regulated in some digestive system tumors, but the expression patterns and pathological role of CMTM7 in gastric cancer remains unclear. In this study, we found that both CMTM7 and SOX10 were significantly down-regulated in gastric cancer tissues compared with paracancerous tissues, and the expression pattern of CMTM7 and SOX10 were strongly correlated (r = 0.6455, p < 0.001). Further, through bioinformatics technology and luciferase assay, we identify that SOX10 can be a transcriptional regulator of CMTM7 to mediate the expression of CMTM7 in gastric cancer. In addition, we found silencing the expression of CMTM7 can increase the proliferation and tumorigenesis of gastric cancer cells in vivo and in vitro. More interestingly, overexpression of SOX10 in cell lines stably silencing CMTM7 expression significantly inhibited the proliferation and tumor growth of gastric cancer. Therefore, our results demonstrate that CMTM7 as a tumor suppressor is down-regulated in gastric cancer, and SOX10 can regulate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7.
大量研究表明 CMTM 家族成员在癌症的发生和进展中具有多种重要作用。CMTM7 也已被报道在一些消化系统肿瘤中下调,但 CMTM7 在胃癌中的表达模式和病理作用尚不清楚。在本研究中,我们发现与癌旁组织相比,胃癌组织中 CMTM7 和 SOX10 的表达均显著下调,且 CMTM7 和 SOX10 的表达模式呈强相关性(r=0.6455,p<0.001)。此外,通过生物信息学技术和荧光素酶检测,我们鉴定出 SOX10 可以作为 CMTM7 的转录调节因子,介导胃癌中 CMTM7 的表达。此外,我们发现沉默 CMTM7 的表达可以增加胃癌细胞在体内和体外的增殖和致瘤能力。更有趣的是,过表达 SOX10 可显著抑制稳定沉默 CMTM7 表达的细胞系中胃癌的增殖和肿瘤生长。因此,我们的结果表明 CMTM7 作为抑癌基因在胃癌中下调,SOX10 可以通过调节 CMTM7 的表达来调节胃癌的增殖和肿瘤形成。