Tian Chao, Zeng Shiyan, Luo Jing
Department of Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, Sichuan, People's Republic of China.
Department of Breast Surgery, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan, People's Republic of China.
Onco Targets Ther. 2020 Jun 10;13:5353-5361. doi: 10.2147/OTT.S255675. eCollection 2020.
MCTS1 re-initiation and release factor (MCTS1) is a ribosome-binding protein and shows multiple oncogenic properties in multiple cancers. This study aimed to investigate the expression, prognostic significance and transcription profile of in the PAM50 subtypes of breast cancer, as well as proteins with functional interactions with MCTS1 in luminal A/B breast cancer cells.
Data from The Cancer Genome Atlas (TCGA)-Breast Carcinoma (BRCA) and Gene Expression Omnibus (GEO) and normal breast epithelial tissue data from the Genotype-Tissue Expression (GTEx) project were extracted and integrated for bioinformatic analysis. BT-474 and MCF-7 cells were used for in-vitro studies.
expression varied significantly among PAM50 subtypes. Its expression might independently predict unfavorable overall survival (OS) in luminal A and B cases, but not in other subtypes. ENST00000371317.9 is the dominant isoform of transcripts and showed a step increase from normal, adjacent normal to breast cancer tissues. The protein encoded by this isoform directly bound to TWF1 and synergistically modulated cyclin D1 and C-Myc translation in BT-474 and MCF-7 cells.
expression might serve as a potential prognostic biomarker of unfavorable OS in luminal A and luminal B cases. The novel direct interaction between MCTS1 and TWF1 might be necessary for the translation of some downstream genes in common in luminal A/B breast cancer cells.
MCTS1重新起始和释放因子（MCTS1）是一种核糖体结合蛋白，在多种癌症中表现出多种致癌特性。本研究旨在调查MCTS1在乳腺癌PAM50亚型中的表达、预后意义和转录谱，以及在腔面A/B型乳腺癌细胞中与MCTS1具有功能相互作用的蛋白质。
提取并整合来自癌症基因组图谱（TCGA）-乳腺癌（BRCA）和基因表达综合数据库（GEO）的数据以及来自基因型-组织表达（GTEx）项目的正常乳腺上皮组织数据，进行生物信息学分析。使用BT-474和MCF-7细胞进行体外研究。
MCTS1在PAM50亚型中的表达差异显著。其表达可能独立预测腔面A和B型病例的不良总生存期（OS），但在其他亚型中并非如此。ENST00000371317.9是MCTS1转录本的主要异构体，从正常组织、癌旁正常组织到乳腺癌组织呈逐步增加。该异构体编码的蛋白质直接与TWF1结合，并在BT-474和MCF-7细胞中协同调节细胞周期蛋白D1和C-Myc的翻译。
MCTS1表达可能是腔面A和腔面B型病例不良OS的潜在预后生物标志物。MCTS1与TWF1之间新发现的直接相互作用可能是腔面A/B型乳腺癌细胞中一些常见下游基因翻译所必需的。
