Anita Ramesh, Paramasivam Arumugam, Priyadharsini Jayaseelan Vijayashree, Chitra Srinivasan
Department of Medical Oncology, Saveetha Medical College Hospital, Saveetha University Chennai, India.
BRULAC-DRC, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University Chennai, India.
Am J Cancer Res. 2020 Aug 1;10(8):2546-2554. eCollection 2020.
N6-Methyladenosine (m6A) is the most common RNA modification in eukaryotic mRNAs and growing evidence suggests the crucial roles of m6A and its regulators in human tumorigenesis. Recent studies have shown that the m6A regulators promote tumorigenesis of various types of cancer. However, the underlying molecular mechanisms of m6A regulators in breast cancer remain largely unknown. We therefore assessed the genetic alterations, expression and prognostic role of m6A regulators in breast cancer using openly available data from The Cancer Genome Atlas (TCGA). Analysis of TCGA data revealed that m6A regulators including , , and were upregulated in breast cancer tissues, and the expression level significantly correlated with intrinsic subclasses and nodal metastasis. Importantly, we found for the first time that and were frequently amplified which contribute to the overexpression of and transcripts, thereby promoting breast cancer progression. Moreover, overexpression of and were associated with poor prognosis of breast cancer patients. Therefore, YTHDF1 and YTHDF3 serve a crucial role in the pathogenesis of breast cancer, which are potentially useful for prognosis stratification and therapeutic target for breast cancer.
N6-甲基腺苷(m6A)是真核生物信使核糖核酸(mRNA)中最常见的RNA修饰,越来越多的证据表明m6A及其调节因子在人类肿瘤发生中起关键作用。最近的研究表明,m6A调节因子促进各种类型癌症的肿瘤发生。然而,m6A调节因子在乳腺癌中的潜在分子机制仍 largely未知。因此,我们使用来自癌症基因组图谱(TCGA)的公开可用数据评估了m6A调节因子在乳腺癌中的基因改变、表达和预后作用。对TCGA数据的分析显示,包括 、 和 的m6A调节因子在乳腺癌组织中上调,且表达水平与内在亚类和淋巴结转移显著相关。重要的是,我们首次发现 和 经常扩增,这导致 和 转录本的过表达,从而促进乳腺癌进展。此外, 和 的过表达与乳腺癌患者的不良预后相关。因此,YTHDF1和YTHDF3在乳腺癌发病机制中起关键作用,这可能对乳腺癌的预后分层和治疗靶点有用。 (注:原文中部分调节因子名称未给出完整,翻译时保留原文格式)