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RDM1 促进乳腺癌肿瘤发生中的关键过程。

RDM1 promotes critical processes in breast cancer tumorigenesis.

机构信息

Department of Clinical Laboratory, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Department of Musculoskeletal Tumor, Shanghai Cancer Center, Fudan University, Shanghai, China.

出版信息

J Cell Mol Med. 2019 Aug;23(8):5432-5439. doi: 10.1111/jcmm.14425. Epub 2019 Jun 20.

Abstract

Breast cancer is currently among the most common cancers in women, with almost 200,000 new cases diagnosed annually. Dysregulation of DNA repair pathways allows cells to accumulate damage and eventually mutations, with a subsequent reduction in DNA repair capacity in breast tissue, leading to tumorigenesis. One component of the DNA damage repair pathway is RAD52 motif-containing 1 (RDM1), but the specific role of RDM1 in breast cancer and the underlying mechanism remain unclear. Here, we examined the role played by RDM1 in breast cancer cell culture using the HBL100 and MCF-7 breast cancer cell lines. Disruption of RDM1 reduced in vitro cell proliferation and promoted apoptosis. Knockdown of RDM1 also induced up-regulation of p53 levels, whereas RAD51 and RAD52, both involved in DNA repair, were down-regulated. In addition, the in vivo growth of RDM1-deficient cells was significantly repressed, suggesting that RDM1 is a novel oncogenic protein in human breast cancer cells. This study reveals a link between the DNA damage response pathway and oncogenic functionality in breast cancer. Accordingly, therapeutic targeting of RDM1 is a potential treatment strategy for breast cancer and overcoming drug resistance.

摘要

乳腺癌是目前女性最常见的癌症之一,每年约有 20 万例新发病例。DNA 修复途径的失调使细胞能够积累损伤,最终导致突变,从而降低乳腺组织的 DNA 修复能力,导致肿瘤发生。DNA 损伤修复途径的一个组成部分是 RAD52 结构域包含蛋白 1(RDM1),但 RDM1 在乳腺癌中的具体作用及其潜在机制尚不清楚。在这里,我们使用 HBL100 和 MCF-7 乳腺癌细胞系研究了 RDM1 在乳腺癌细胞培养中的作用。RDM1 的破坏减少了体外细胞增殖并促进了细胞凋亡。RDM1 的敲低还诱导了 p53 水平的上调,而 RAD51 和 RAD52,都参与 DNA 修复,下调。此外,RDM1 缺失细胞的体内生长明显受到抑制,表明 RDM1 是人类乳腺癌细胞中的一种新型致癌蛋白。这项研究揭示了 DNA 损伤反应途径与乳腺癌致癌功能之间的联系。因此,针对 RDM1 的治疗靶向可能是治疗乳腺癌和克服耐药性的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1051/6653204/c802b423526f/JCMM-23-5432-g001.jpg

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