MiR-10a functions as a tumor suppressor in prostate cancer via targeting KDM4A
| Autor: | Luxia Xiang, Shuaibin Wang, Shaoxun Li, Dapang Rao, Kaiyuan Yu, Haiqi Mu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Jumonji Domain-Containing Histone Demethylases Mice Nude Biochemistry law.invention 03 medical and health sciences Prostate cancer Mice 0302 clinical medicine Western blot Downregulation and upregulation law microRNA medicine Animals Humans Luciferase Genes Tumor Suppressor RNA Neoplasm Molecular Biology Adaptor Proteins Signal Transducing medicine.diagnostic_test Cell growth Chemistry Prostatic Neoplasms YAP-Signaling Proteins Cell Biology medicine.disease MicroRNAs 030104 developmental biology Cell culture 030220 oncology & carcinogenesis PC-3 Cells Cancer research Suppressor Heterografts Neoplasm Transplantation Signal Transduction Transcription Factors |
| Zdroj: | Journal of cellular biochemistry. 120(4) |
| ISSN: | 1097-4644 |
| Popis: | Deregulation of microRNAs contributes to the abnormal cell growth which is frequently observed in cancer. In the current study, we detected the expression and regulatory relationship between miR-10a and Lysine-specific demethylase 4A (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found that miR-10a levels were significantly decreased in PCa cell lines in comparison with the normal epithelial cell line RWPE-1. Downregulation of miR-10a levels was also observed in tumor tissues from PCa patients compared with the adjacent normal tissues. Enhanced expression of miR-10a inhibited cell proliferation and colony forming capability of PCa cells. In addition, quantitative real-time polymerase chain reaction and Western blot analysis showed a significant decrease of KDM4A in response to miR-10a elevation in PCa cells. Using dual luciferase assay, we confirmed that KDM4A was a target gene for miR-10a. Furthermore, Western blot analysis indicated that miR-10a overexpression inactivated YAP signaling and suppressed transcription of YAP target genes. Additionally, cell growth arrest and colony forming capacity inhibition induced by miR-10a overexpression could be reversed by YAP overexpression in PCa cells. More importantly, miR-10a mimics inhibited PC-3 tumor growth in nude mice accompanied with a remarkable reduction of KDM4A and YAP expression. In conclusion, our results uncovered a tumor suppressor role of miR-10a in PCa via negative regulation of KDM4A and its downstream Hippo-YAP pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text