Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), 200025, Shanghai, China.
Cell Death Dis. 2018 Jul 3;9(7):752. doi: 10.1038/s41419-018-0715-6.
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.
miR-133b 是一种普遍被认可的肌肉特异性 miRNA，据报道在许多类型的癌症中失调。然而，其在肿瘤发生中的潜在作用仍然很大程度上难以捉摸。在此，我们证明 miR-133b 在人类乳腺癌标本中显著受抑制，与癌症的组织学分级呈负相关。miR-133b 的异位表达抑制了体外的集落形成能力和转移相关特征，以及体内的致癌作用和肺转移。进一步的研究已经确定 Sox9、c-MET 和 WAVE2 是 miR-133b 的直接靶标，其中 Sox9 有助于 miR-133b 赋予的所有效应，包括细胞增殖、集落形成以及体外的细胞迁移和侵袭。此外，Sox9 的重新表达逆转了 miR-133b 介导的体内转移抑制。总之，这些发现强调了 miR-133b 在调节乳腺癌的肿瘤发生和转移潜能中的重要作用，并提示 miR-133b 在癌症治疗中的潜在应用。
