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
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2015 Apr 29;10(4):e0124410. doi: 10.1371/journal.pone.0124410. eCollection 2015.
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.
微小(mi)RNA是参与包括癌症在内的各种生理和病理过程的重要调节因子。miRNA - 302家族已被证明在致癌过程中起关键作用。在本研究中,我们调查了miRNA - 302a在前列腺癌(PCa)中的作用。检测了44例PCa组织和10例正常前列腺组织中miRNA - 302a的表达,并分析了其临床病理意义。对稳定表达miRNA - 302a的PCa细胞进行细胞增殖和细胞周期分析。进一步研究了miRNA - 302a的靶基因及其下游途径。与正常前列腺组织相比,PCa组织中miRNA - 302a表达下调,在Gleason评分≥8的PCa组织中甚至更低。miRNA - 302a的过表达诱导PCa细胞G1/S期细胞周期阻滞,并在体外和体内抑制PCa细胞增殖。此外,miRNA - 302a通过直接结合其3΄非翻译区抑制AKT表达,导致随后AKT - GSK3β - 细胞周期蛋白D1和AKT - p27Kip1途径的改变。这些结果揭示了miRNA - 302a在PCa中作为肿瘤抑制因子的作用,表明miRNA - 302a可能作为PCa治疗干预的潜在靶点。