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.
Highlights
Breast cancer is one of the most common cancers with>1,300,000 cases and 450,000 deaths each year worldwide[1]
MiR-133b expression is downregulated in breast cancer We first evaluated the expression of miR-133b in human mammary cell lines by the quantitative RT-PCR analysis
To further describe miR-133b expression levels within mammary epithelial cells in the context of mammary architecture, we applied in situ hybridization with a miR133b-locked nucleic acid (LNA) probe on breast cancer microarray sections
Summary
Breast cancer is one of the most common cancers with>1,300,000 cases and 450,000 deaths each year worldwide[1]. Like many other solid tumors, metastasis is responsible for as much as 90% of breast cancer-related mortality[2]. The invasion–metastasis cascade encompasses multistep process involving local invasion, intravasation, survival in the circulation, extravasation, micrometastasis, colonization, and outgrowth of secondary tumors[3]. Metastasis is a highly inefficient process, and only a few cells are believed to be able to complete all the steps and develop. An individual miRNA can regulate dozens of distinct mRNAs and bioinformatics predictions reveal that more than one-third of the protein-coding genes are regulated by miRNAs11. MiRNAs play important roles in various biological processes, such as cellular differentiation, proliferation, apoptosis, as well as stem cell maintenance, and their deregulation are associated with the development of various diseases including
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