MicroRNA-302a Suppresses Tumor Cell Proliferation by Inhibiting AKT in Prostate Cancer

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124410
• Main Authors: Zhang, Gui-Ming, Bao, Chun-Yang, Wan, Fang-Ning, Cao, Da-Long, Qin, Xiao-Jian, Zhang, Hai-Liang, Zhu, Yao, Dai, Bo, Shi, Guo-Hai, Ye, Ding-Wei
• Format: Article
• Language: English
• Subjects: AKT protein; Animals; Apoptosis; Binding sites; Cancer; Cancer therapies; Carcinogenesis; Carcinogens; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Colorectal cancer; Cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin-dependent kinase inhibitor p27; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic; Genetic Vectors - administration & dosage; Genetic Vectors - metabolism; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; HEK293 Cells; Humans; Lentivirus - genetics; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplasm Grading; Neoplasm Transplantation; Polymerase chain reaction; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Regulators; Ribonucleic acid; RNA; Signal Transduction; Stem cells; Tissues; Tumor suppressor genes; Tumorigenesis; Tumors; Urology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124410

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.