Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, Wenhua West Road No. 107, Ji'nan, Shandong, 250012, P. R. China.
Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, 250012,, Shandong Province, People's Republic of China.
Cell Death Dis. 2018 Jan 11;9(1):14. doi: 10.1038/s41419-017-0030-7.
Chemo-resistance and metastasis of triple negative breast cancer (TNBC) contributed the most of treatment failure in the clinic. MicroRNAs (miRNAs) have been proved to be involved in many biological processes and diseases. In this study, we aimed to determine the role of miR-770 in the regulation of chemo-resistance and metastasis of TNBC. Clinically, miR-770 was highly expressed in chemo-sensitive tissues and predicted a better prognosis of TNBC. Functionally, ectopic expression of miR-770 suppressed the doxorubicin-resistance of TNBC cell lines via regulation of apoptosis and tumor microenvironment, which was mediated by exosomes. Moreover, miR-770 overexpression inhibited the migration and invasion. Rescue of STMN1 could partly reverse the effect of miR-770 in TNBC behaviors. Furthermore, we also demonstrated that overexpression of miR-770 inhibited DOX resistance and metastasis in vivo. Taken together, our results proved that miR-770 could suppress the doxorubicin-resistance and metastasis of TNBC cells, which broaden our insights into the underlying mechanisms in chemo-resistance and metastasis, and provided a new prognostic marker for TNBC cells.
三阴性乳腺癌（TNBC）的化疗耐药和转移是临床治疗失败的主要原因。 microRNAs（miRNAs）已被证明参与许多生物过程和疾病。在本研究中，我们旨在确定 miR-770 在调节 TNBC 的化疗耐药和转移中的作用。临床上，miR-770 在化疗敏感组织中高表达，并预测 TNBC 的预后较好。功能上，miR-770 的异位表达通过调节细胞凋亡和肿瘤微环境抑制 TNBC 细胞系的多柔比星耐药，这是由外泌体介导的。此外，miR-770 的过表达抑制迁移和侵袭。STMN1 的恢复可以部分逆转 miR-770 在 TNBC 行为中的作用。此外，我们还证明了 miR-770 的过表达抑制了体内多柔比星耐药和转移。综上所述，我们的研究结果表明，miR-770 可以抑制 TNBC 细胞的多柔比星耐药和转移，这拓宽了我们对化疗耐药和转移潜在机制的认识，并为 TNBC 细胞提供了一个新的预后标志物。
