MicroRNA-302a Suppresses Tumor Cell Proliferation by Inhibiting AKT in Prostate Cancer
Autor: | Yao Zhu, Bo Dai, Chun Yang Bao, Hai Liang Zhang, Dingwei Ye, Fang Ning Wan, Da Long Cao, Guo Hai Shi, Xiao Jian Qin, Gui Ming Zhang |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Male
Genetic Vectors lcsh:Medicine Mice Nude Apoptosis Biology medicine.disease_cause urologic and male genital diseases Prostate cancer Glycogen Synthase Kinase 3 Prostate Cell Line Tumor microRNA medicine Animals Humans Cyclin D1 lcsh:Science Protein kinase B Cell Proliferation Regulation of gene expression Mice Inbred BALB C Multidisciplinary Glycogen Synthase Kinase 3 beta Cell growth lcsh:R Lentivirus Cancer Prostatic Neoplasms Correction medicine.disease G1 Phase Cell Cycle Checkpoints Gene Expression Regulation Neoplastic MicroRNAs medicine.anatomical_structure HEK293 Cells Cancer research lcsh:Q Neoplasm Grading Carcinogenesis Proto-Oncogene Proteins c-akt Cyclin-Dependent Kinase Inhibitor p27 Neoplasm Transplantation Signal Transduction Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 4, p e0124410 (2015) |
ISSN: | 1932-6203 |
Popis: | Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa. |
Databáze: | OpenAIRE |
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