BMP-6 inhibits cell proliferation by targeting microRNA-192 in breast cancer.

Abstract

Although bone morphogenetic protein-6 (BMP-6) has been identified as a tumor suppressor associated with breast cancer differentiation and metastasis, the potential roles of BMP-6 in regulating cell cycle progression have not been fully examined. In the present study, we provide the novel finding that induction of BMP-6 in MDA-MB-231 breast cancer cells significantly inhibits cell proliferation by decreasing the number of cells in S phase of the cell cycle, resulting in inhibition of tumorigenesis in a nude mouse xenograft model. Further investigation indicated that BMP-6 up-regulates the expression of microRNA-192 (miR-192) in MDA-MB-231 cells. Elevated expression of miR-192 caused cell growth arrest, which is similar to the effect of BMP-6 induction. Importantly, depletion of endogenous miR-192 by miRNA inhibition significantly attenuated BMP-6-mediated repression of cell cycle progression. In breast cancer tissue, miR-192 expression is significantly down-regulated in tumor samples and positively correlates with the expression of BMP-6, demonstrating the inhibitory effect of BMP-6 on cell proliferation through miR-192 regulation. Additionally, using the RT(2) Profiler PCR Array, retinoblastoma 1 (RB1) was identified as a direct target of the BMP-6/miR-192 pathway in regulating cell proliferation in breast cancer. In conclusion, we have identified an important role for BMP-6/miR-192 signaling in the regulation of cell cycle progression in breast cancer. Furthermore, BMP-6/miR-192 was expressed at low levels in breast cancer specimens, indicating that this pathway might represent a promising therapeutic target for breast cancer treatment.

• Authors: Fen Hu, Xiangzhi Meng, Qi Tong, Lin Liang, Rong Xiang, Tianhui Zhu, Shuang Yang
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1832 Issue 12 Pg. 2379-90 (Dec 2013) ISSN: 0006-3002 [Print] Netherlands
• PMID: 24012720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• BMP6 protein, human
• Bone Morphogenetic Protein 6
• MIRN192 microRNA, human
• MicroRNAs
• RNA, Messenger
• Luciferases

Topics

• Animals
• Apoptosis
• Blotting, Western
• Bone Morphogenetic Protein 6 (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Ductal, Breast (genetics, metabolism, pathology)
• Cell Cycle
• Cell Proliferation
• Female
• Humans
• Immunoenzyme Techniques
• Luciferases (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction