Duan Jicheng, Qian Youwen, Fu Xiaohui, Chen Meiling, Liu Kai, Liu Hu, Yang Jiahe, Liu Chen, Chang Yanxin
Biliary Tract Surgery Department, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China.
Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China.
Aging (Albany NY). 2021 Feb 11;13(4):5585-5606. doi: 10.18632/aging.202487.
Transmembrane protein (TMEM) is a kind of integral membrane protein that spans biological membranes. The functions of most members of the TMEM family are unknown. Here, we conducted bioinformatic analysis and biological validation to investigate the role of TMEM106C in HCC. First, GEPIA and Oncomine were used to analyze TMEM106C expression, which was verified by real-time PCR and western blot analyses. Then, the biological functions of TMEM106C were explored by CCK8 and transwell assays. The prognostic value of TMEM106C was analyzed by UALCAN. LinkedOmics was used to analyze TMEM106C pathways generated by Gene Ontology. A protein-protein interaction network (PPI) was constructed by GeneMANIA. We demonstrated that TMEM106C was overexpressed in HCC and that inhibition of TMEM106C significantly suppressed the proliferation and metastasis of HCC through targeting CENPM and DLC-1. Upregulation of TMEM106C was closely correlated with sex, tumor stage, tumor grade and prognosis. Overexpression of TMEM106C was linked to functional networks involving organelle fission and cell cycle signaling pathways through the regulation of CDK kinases, E2F1 transcription factors and miRNAs. Our data demonstrated that TMEM106C contributes to malignant characteristics and poor prognosis in HCC, which may serve as a prognostic biomarker and potential therapeutic target.
跨膜蛋白（TMEM）是一类跨越生物膜的整合膜蛋白。TMEM家族大多数成员的功能尚不清楚。在此，我们进行了生物信息学分析和生物学验证，以研究TMEM106C在肝癌中的作用。首先，使用GEPIA和Oncomine分析TMEM106C的表达，并通过实时PCR和蛋白质印迹分析进行验证。然后，通过CCK8和Transwell实验探究TMEM106C的生物学功能。利用UALCAN分析TMEM106C的预后价值。使用LinkedOmics分析由基因本体论生成的TMEM106C途径。通过GeneMANIA构建蛋白质-蛋白质相互作用网络（PPI）。我们证明TMEM106C在肝癌中过表达，并且抑制TMEM106C通过靶向CENPM和DLC-1显著抑制肝癌的增殖和转移。TMEM106C的上调与性别、肿瘤分期、肿瘤分级和预后密切相关。通过调节CDK激酶、E2F1转录因子和miRNA，TMEM106C的过表达与涉及细胞器分裂和细胞周期信号通路的功能网络相关。我们的数据表明，TMEM106C促进肝癌的恶性特征和不良预后，其可能作为一种预后生物标志物和潜在的治疗靶点。
