Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China.
Yunnan Collaborative Innovation Center for Plateau Lake Ecology and Environmental Health, Kunming 650214, China.
Int J Mol Sci. 2023 May 27;24(11):9360. doi: 10.3390/ijms24119360.
Breast cancer is the most prevalent cancer in the world. Currently, the main treatments for breast cancer are radiotherapy, chemotherapy, targeted therapy and surgery. The treatment measures for breast cancer depend on the molecular subtype. Thus, the exploration of the underlying molecular mechanisms and therapeutic targets for breast cancer remains a hotspot in research. In breast cancer, a high level of expression of DNMTs is highly correlated with poor prognosis, that is, the abnormal methylation of tumor suppressor genes usually promotes tumorigenesis and progression. MiRNAs, as non-coding RNAs, have been identified to play key roles in breast cancer. The aberrant methylation of miRNAs could lead to drug resistance during the aforementioned treatment. Therefore, the regulation of miRNA methylation might serve as a therapeutic target in breast cancer. In this paper, we reviewed studies on the regulatory mechanisms of miRNA and DNA methylation in breast cancer from the last decade, focusing on the promoter region of tumor suppressor miRNAs methylated by DNMTs and the highly expressed oncogenic miRNAs inhibited by DNMTs or activating TETs.
乳腺癌是世界上最常见的癌症。目前,乳腺癌的主要治疗方法有放疗、化疗、靶向治疗和手术。乳腺癌的治疗措施取决于分子亚型。因此,探索乳腺癌的潜在分子机制和治疗靶点仍然是研究的热点。在乳腺癌中,DNMTs 的高表达与预后不良高度相关,即肿瘤抑制基因的异常甲基化通常会促进肿瘤发生和进展。miRNAs 作为非编码 RNA,已被确定在乳腺癌中发挥关键作用。miRNAs 的异常甲基化可能导致上述治疗过程中的耐药性。因此,miRNA 甲基化的调控可能成为乳腺癌的治疗靶点。本文综述了近十年来 miRNA 和 DNA 甲基化在乳腺癌中的调控机制研究,重点关注 DNMTs 甲基化的肿瘤抑制 miRNA 的启动子区域和被 DNMTs 抑制或激活 TETs 的高表达致癌 miRNA。