Fan Chunni, Liu Ning, Zheng Dan, Du Jianshi, Wang Keren
Department of Breast Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, People's Republic of China.
Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, People's Republic of China.
Cancer Manag Res. 2019 Jul 22;11:6755-6764. doi: 10.2147/CMAR.S199027. eCollection 2019.
Breast cancer (BC) is a common malignancy in women, but the survival rate for BC is not very encouraging. Especially for triple-negative breast cancer (TNBC), a kind of breast cancer that does not have any of the receptors that are commonly found in BC. We investigated the impact of microRNA-206 (miR-206) on transmembrane 4 L6 family member 1 (TM4SF1) in TNBC for therapeutic purpose. Twenty BC tissues from diagnosed BC patients were analyzed via real-time PCR and Western blotting for expression of TM4SF1 and miR-206. The expression of TM4SF1 was studied in relationship with miR-206 in MDA-MB-231 cells. The biological impact of TM4SF1 and miR-206 on MDA-MB-231 cells and BALB/c nude mice model was studied using proliferation, transwell migration, and invasion assays both in vitro and in vivo. The expression of TM4SF1 in BC tissues was significantly higher than that in adjacent normal breast tissues. In contrast, miR-206 showed a decreased expression level in BC tissues, especially for subtype basal like. Overexpression of miR-206 in MDA-MB-231 cells by transfecting miR-206 resulted in downregulation of TM4SF1. In contrast, knockdown miR-206 expression reversed miR-206-mediated phenotype in MDA-MB-231 cells. Expression level of TM4SF1 in MDA-MB-231 cells was associated with cell migration and invasion capabilities in vitro. Breast tumor burden was correlated with the expression level of TM4SF1 in vivo. Taken together, our results showed the involvement of TM4SF1 in TNBC migration and invasion. miR-206 negatively regulated gene expression of TM4SF1. These findings indicate that miR-206 could be used as a potential therapeutic agent for TNBC.
乳腺癌（BC）是女性常见的恶性肿瘤，但BC的生存率并不乐观。特别是三阴性乳腺癌（TNBC），这是一种在BC中通常不存在任何常见受体的乳腺癌。为了治疗目的，我们研究了微小RNA-206（miR-206）对TNBC中跨膜4 L6家族成员1（TM4SF1）的影响。通过实时PCR和蛋白质印迹法分析了20例确诊为BC患者的BC组织中TM4SF1和miR-206的表达。研究了MDA-MB-231细胞中TM4SF1与miR-206的表达关系。使用体外和体内的增殖、Transwell迁移和侵袭试验研究了TM4SF1和miR-206对MDA-MB-231细胞和BALB/c裸鼠模型的生物学影响。BC组织中TM4SF1的表达明显高于相邻正常乳腺组织。相反，miR-206在BC组织中的表达水平降低，尤其是基底样亚型。通过转染miR-206使MDA-MB-231细胞中miR-206过表达导致TM4SF1下调。相反，敲低miR-206表达可逆转miR-206介导的MDA-MB-231细胞表型。MDA-MB-231细胞中TM4SF1的表达水平与体外细胞迁移和侵袭能力相关。体内乳腺肿瘤负荷与TM4SF1的表达水平相关。综上所述，我们的结果表明TM4SF1参与TNBC的迁移和侵袭。miR-206负调控TM4SF1的基因表达。这些发现表明miR-206可作为TNBC的潜在治疗药物。
