1. MiR-133b targets Sox9 to control pathogenesis and metastasis of breast cancer.
- Author
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Wang QY, Zhou CX, Zhan MN, Tang J, Wang CL, Ma CN, He M, Chen GQ, He JR, and Zhao Q
- Subjects
- Breast Neoplasms genetics, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic genetics, Humans, In Vitro Techniques, MicroRNAs genetics, Neoplasm Metastasis genetics, Neoplasm Metastasis pathology, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins c-met metabolism, SOX9 Transcription Factor genetics, Wiskott-Aldrich Syndrome Protein Family genetics, Wiskott-Aldrich Syndrome Protein Family metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, MicroRNAs metabolism, SOX9 Transcription Factor metabolism
- Abstract
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.
- Published
- 2018
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