Gu Shuo, Niu Xiaobing, Mao Fei, Xu Zongyuan
Department of Urology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University No. 1, West Huanghe Road, Huaiyin District Huaian City Jiangsu Province 223300 P. R. China
RSC Adv. 2018 Nov 8;8(66):37564-37572. doi: 10.1039/c8ra08083f. eCollection 2018 Nov 7.
Prostate cancer is one of the common tumor malignancies in men worldwide. Although long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in the progression of prostate cancer, the roles and potential mechanism of lncRNA prostate cancer antigen 3 (PCA3) remain poorly understood. In the present study, we investigated the role of PCA3 in aerobic glycolysis, viability and apoptosis in prostate cancer cells and probed the interaction between PCA3 and microRNA-1 (miR-1)/cyclin-dependent kinase 4 (CDK4). Here we found that PCA3 and CDK4 were up-regulated while miR-1 was down-regulated in prostate cancer tissues and cells. Moreover, knockdown of PCA3 inhibited aerobic glycolysis and viability and induced apoptosis in prostate cancer cells. Intriguingly, PCA3 was bound to miR-1 and inhibition of miR-1 reversed the regulatory effect of PCA3 knockdown on aerobic glycolysis, viability and apoptosis in prostate cancer cells. Besides, CDK4 was indicated as a target of miR-1 and it was regulated by PCA3 through functioning as a competing endogenous RNA (ceRNA) of miR-1 in prostate cancer cells. The results indicated that PCA3 might drive aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells, providing a promising avenue for treatment of prostate cancer.
前列腺癌是全球男性常见的肿瘤恶性疾病之一。尽管长链非编码RNA（lncRNAs）已被证明在前列腺癌进展中发挥重要作用，但lncRNA前列腺癌抗原3（PCA3）的作用及潜在机制仍知之甚少。在本研究中，我们调查了PCA3在前列腺癌细胞有氧糖酵解、活力和凋亡中的作用，并探究了PCA3与微小RNA-1（miR-1）/细胞周期蛋白依赖性激酶4（CDK4）之间的相互作用。在此我们发现，在前列腺癌组织和细胞中，PCA3和CDK4上调，而miR-1下调。此外，敲低PCA3可抑制前列腺癌细胞的有氧糖酵解和活力，并诱导其凋亡。有趣的是，PCA3与miR-1结合，抑制miR-1可逆转PCA3敲低对前列腺癌细胞有氧糖酵解、活力和凋亡的调节作用。此外，CDK4被表明是miR-1的靶点，在前列腺癌细胞中，PCA3通过作为miR-1的竞争性内源RNA（ceRNA）发挥作用来调控CDK4。结果表明，PCA3可能通过调节前列腺癌细胞中的miR-1/CDK4轴来驱动有氧糖酵解、活力和凋亡，为前列腺癌的治疗提供了一条有前景的途径。
