MiR-133b targets Sox9 to control pathogenesis and metastasis of breast cancer

作者：Qiuyu Wang, Ci-Xiang Zhou, Mengna Zhan, Jun Tang, Chen-Long Wang, Cheng-Ning Ma, Ming He, Guoqiang Chen, Jianrong He, Qian Zhao · 发表于：Cell Death and Disease · 年份：2018 · DOI：10.1038/s41419-018-0715-6 · 被引用次数：61 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、Circular RNAs in diseases

The miR-133b, a commonly recognized muscle-specific miRNA, was reported to be deregulated in many kinds of cancers. However, its potential roles in tumorigenesis remain greatly elusive. Herein, we demonstrate that miR-133b is significantly suppressed in human breast cancer specimens, which is reversely correlated to histological grade of the cancer. Ectopic expression of miR-133b suppresses clonogenic ability and metastasis-relevant traits in vitro, as well as carcinogenesis and pulmonary metastasis in vivo. Further studies have identified Sox9, c-MET, and WAVE2 as direct targets of miR-133b, in which Sox9 contributes to all miR-133b-endowed effects including cell proliferation, colony formation, as well as cell migration and invasion in vitro. Moreover, re-expression of Sox9 reverses miR-133b-mediated metastasis suppression in vivo. Taken together, these findings highlight an important role for miR-133b in the regulation of tumorigenesis and metastatic potential of breast cancer and suggest a potential application of miR-133b in cancer treatment.