Zhang Li, Ma Ping, Sun Li-Mei, Han Yan-Chun, Li Bai-Lin, Mi Xiao-Yi, Wang En-Hua, Song Min
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Heping District, Shenyang, China.
The second laboratory of Cancer Research Institute, First Affiliated Hospital, China Medical University, Heping District, Shenyang, China.
Mol Carcinog. 2016 May;55(5):768-77. doi: 10.1002/mc.22320. Epub 2015 Apr 7.
We have reported that SIAH1 is down-regulated and associated with apoptosis and invasion in human breast cancer. However, the molecular mechanisms leading to SIAH1 down-regulation remain to be elucidated. Here, we demonstrated that miR-107 directly down-regulates SIAH1 expression in human breast cancer cells. Over- expression of miR-107 reduced SIAH1 expression, promoted human breast cancer cell proliferation, colony formation, migration and invasion, and inhibited apoptosis. On the contrary, silencing of miR-107 increased SIAH1 expression and inhibited the tumor growth of MDA-MB-231 cells, a kind of triple-negative breast cancer (TNBC) cells, in vitro and in vivo. Our results reveal that miR-107 is an upstream regulator for SIAH1 down-regulation in human breast cancer cells and miR-107 provides a potential effective target for the treatment of TNBC.
我们曾报道,SIAH1在人类乳腺癌中表达下调,且与细胞凋亡和侵袭相关。然而,导致SIAH1下调的分子机制仍有待阐明。在此,我们证明了miR-107可直接下调人类乳腺癌细胞中SIAH1的表达。miR-107的过表达降低了SIAH1的表达,促进了人类乳腺癌细胞的增殖、集落形成、迁移和侵袭,并抑制了细胞凋亡。相反,miR-107的沉默增加了SIAH1的表达,并在体外和体内抑制了三阴性乳腺癌(TNBC)细胞系MDA-MB-231细胞的肿瘤生长。我们的结果表明,miR-107是人类乳腺癌细胞中SIAH1下调的上游调节因子,并且miR-107为TNBC的治疗提供了一个潜在的有效靶点。