MCTS1 Directly Binds to TWF1 and Synergistically Modulate Cyclin D1 and C-Myc Translation in Luminal A/B Breast Cancer Cells
MCTS1 Directly Binds to TWF1 and Synergistically Modulate Cyclin D1 and C-Myc Translation in Luminal A/B Breast Cancer Cells
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DOI：
10.2147/ott.s255675
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Luo, Jing
中科院分区：
文献类型：
--
作者：
Tian, Chao;Zeng, Shiyan;Luo, Jing
目的：MCTS 1再起始和释放因子（MCTS 1）是一种核糖体结合蛋白，在多种癌症中显示出多种致癌特性。本研究旨在研究MCTS 1在乳腺癌的PAM 50亚型中的表达、预后意义和转录谱，以及在管腔A/B乳腺癌细胞中与MCTS 1具有功能性相互作用的蛋白。来自癌症基因组图谱（TCGA）的数据-乳腺癌（BRCA）和基因表达综合（GEO）以及来自基因型的正常乳腺上皮组织数据-组织表达（GTEx）项目提取并整合用于生物信息学分析。结果：MCTS 1在不同PAM 50亚型中的表达差异有统计学意义。它的表达可能独立预测管腔A和B型患者的不良总生存期（OS），但在其他亚型中则不然。ENST 00000371317.9是MCTS 1转录物的主要亚型，从正常组织、邻近正常组织到乳腺癌组织呈阶梯式增加。结论：MCTS 1的表达可作为预测Luminal A和Luminal B患者预后不良的生物标志物。MCTS 1和TWF 1之间的这种新的直接相互作用可能是Luminal A/B乳腺癌细胞中一些共同下游基因翻译所必需的。
Purpose: 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 MCTS1 in the PAM50 subtypes of breast cancer, as well as proteins with functional interactions with MCTS1 in luminal A/B breast cancer cells.Materials and Methods: 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.Results: MCTS1 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 MCTS1 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.Conclusion: MCTS1 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.