Wang Zhonglin, Li Shuqin, Xu Feng, Fu Jingyue, Sun Jie, Gan XinLi, Yang Chuang, Mao Zhongqi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Soochow, 215006, China.
Department of Breast Surgery, The Second People's Hospital of Lianyungang, Lianyungang, 222006, China.
Cancer Cell Int. 2022 May 2;22(1):177. doi: 10.1186/s12935-022-02595-x.
Breast cancer is notorious for its increasing incidence for decades. Ascending evidence has demonstrated that translocase of inner mitochondrial membrane (TIMM) proteins play vital roles in progression of several types of human cancer. However, the biological behaviors and molecular mechanisms of TIMM8A in breast cancer remain not fully illustrated.
Pan-cancer analysis was firstly performed for TIMM8A's expression and prognosis by Oncomine database. Subsequently, TIMM8A-related noncoding RNAs (ncRNAs) were identified by a series of bioinformatics analyses and dual-luciferase reporter assay, including expression analysis, correlation analysis, and survival analysis. Moreover, the effect of TIMM8A on breast cancer proliferation and apoptosis was evaluated in vitro by CCK-8 assays, EdU cell proliferation assays, JC-1 mitochondrial membrane potential detection assays and Western blot assays and the in vivo effect was revealed through a patient-derived xenograft mouse model.
We found that TIMM8A showed higher expression level in breast cancer and the higher TIMM8A mRNA expression group had a poorer prognosis than the lower TIMM8A group. hsa-circ-0107314/hsa-circ-0021867/hsa-circ-0122013 might be the three most potential upstream circRNAs of hsa-miR-34c-5p/hsa-miR-449a-TIMM8A axis in breast cancer. TIMM8A promotes proliferation of breast cancer cells in vitro and tumor growth in vivo.
Our results confirmed that ncRNAs-mediated upregulation of TIMM8A correlated with poor prognosis and act as an oncogene in breast cancer.
几十年来，乳腺癌的发病率不断上升，声名狼藉。越来越多的证据表明，线粒体内膜转位酶（TIMM）蛋白在几种人类癌症的进展中起着至关重要的作用。然而，TIMM8A在乳腺癌中的生物学行为和分子机制仍未完全阐明。
首先通过Oncomine数据库对TIMM8A的表达和预后进行泛癌分析。随后，通过一系列生物信息学分析和双荧光素酶报告基因检测，包括表达分析、相关性分析和生存分析，鉴定与TIMM8A相关的非编码RNA（ncRNA）。此外，通过CCK-8检测、EdU细胞增殖检测、JC-1线粒体膜电位检测和蛋白质免疫印迹检测，在体外评估TIMM8A对乳腺癌增殖和凋亡的影响，并通过患者来源的异种移植小鼠模型揭示其体内作用。
我们发现TIMM8A在乳腺癌中表达水平较高，TIMM8A mRNA表达水平较高的组预后比TIMM8A水平较低的组更差。hsa-circ-0107314/hsa-circ-0０21867/hsa-circ-0122013可能是乳腺癌中hsa-miR-34c-5p/hsa-miR-449a-TIMM8A轴的三个最具潜力的上游环状RNA。TIMM8A在体外促进乳腺癌细胞增殖，在体内促进肿瘤生长。
我们的结果证实，ncRNA介导的TIMM8A上调与预后不良相关，并在乳腺癌中作为癌基因发挥作用。
