Pan Jhih-Kai, Lin Cheng-Han, Kuo Yao-Lung, Ger Luo-Ping, Cheng Hui-Chuan, Yao Yun-Chin, Hsiao Michael, Lu Pei-Jung
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of General Surgery, National Cheng Kung University Hospital, Tainan, Taiwan.
Oncogene. 2021 Mar;40(9):1737-1751. doi: 10.1038/s41388-021-01654-3. Epub 2021 Feb 3.
Brian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood-brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.
脑转移在30%的三阴性乳腺癌(TNBC)转移患者中被诊断出来,会导致较差的生存结果。越来越多的证据表明,miRNA参与了乳腺癌脑转移;然而,目前缺乏基于血浆的脑转移预后指标。在本研究中,高水平的miR-211可作为体内脑转移的预后标志物。高表达的miR-211通过增强肿瘤细胞的跨血脑屏障(BBB)迁移、BBB黏附及干性特性,驱动早期和特异性的脑内定植,并导致体内生存较差。SOX11和NGN2是miR-211的下游靶点,在体外和体内均对miR-211介导的TNBC脑转移起负调控作用。最重要的是,高表达的miR-211与TNBC患者的不良生存和脑转移相关。我们的研究结果表明,miR-211可能用作TNBC脑转移的指标。