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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yang, Shuang Zhu, Tianhui Tong, Qi Hu, Fen Liang, Lin Xiang, Rong Meng, Xiangzhi |
| Description | Author Affiliation: Hu F ( Medical College of Nankai University, Tianjin, China) |
| 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. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 12 |
| Volume Number | 1832 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-12-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Bone Morphogenetic Protein 6 Metabolism Breast Neoplasms Pathology Carcinoma, Ductal, Breast Cell Proliferation MicroRNAs Genetics Animals Apoptosis Blotting, Western Cell Cycle Immunoenzyme Techniques Luciferases Mice Mice, Inbred BALB C Mice, Nude RNA, Messenger Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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