Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Urology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
Oncol Rep. 2019 Sep;42(3):991-1004. doi: 10.3892/or.2019.7231. Epub 2019 Jul 11.
Previous researchers have demonstrated that microRNA‑505 (miR‑505) is negatively correlated with progression in various malignancies. However, the detailed function and molecular mechanisms of miR‑505 have yet to be completely elucidated in prostate cancer (PCa). The present study initially identified the potential role of miR‑505 in PCa using in vitro experiments, and demonstrated that restoration of miR‑505 inhibited proliferation, invasion and migration, yet induced cell cycle arrest and promoted apoptosis in PCa cells. The present study also demonstrated that the expression of neuron‑glial‑related cell adhesion molecule (NRCAM) was markedly upregulated in PCa cells when compared with benign prostate epithelium. A luciferase reporter assay demonstrated that miR‑505 directly targeted NRCAM in PCa cells. In addition, NRCAM stimulation antagonized the inhibitory effects of miR‑505 on the proliferation, migration, and invasion of PCa cells. Furthermore, lower levels of miR‑505 and higher levels of NRCAM may serve as a predictor of worse biochemical recurrence‑free survival or disease‑free survival in patients with PCa. In conclusion, the present study revealed the inhibitory effects of miR‑505 on PCa tumorigenesis, which potentially occur by targeting NRCAM. The combined analysis of NRCAM and miR‑505 may predict disease progression in patients with PCa following radical prostatectomy.
先前的研究人员已经证实,微小 RNA-505(miR-505)与各种恶性肿瘤的进展呈负相关。然而,miR-505 在前列腺癌(PCa)中的详细功能和分子机制尚未完全阐明。本研究最初通过体外实验确定了 miR-505 在 PCa 中的潜在作用,并且证明恢复 miR-505 抑制了 PCa 细胞的增殖、侵袭和迁移,同时诱导了细胞周期停滞并促进了细胞凋亡。本研究还表明,与良性前列腺上皮相比,神经胶质相关细胞粘附分子(NRCAM)在 PCa 细胞中的表达明显上调。荧光素酶报告基因检测表明,miR-505 可直接靶向 PCa 细胞中的 NRCAM。此外,NRCAM 刺激拮抗了 miR-505 对 PCa 细胞增殖、迁移和侵袭的抑制作用。此外,miR-505 水平降低和 NRCAM 水平升高可能成为预测 PCa 患者生化无复发生存或无病生存较差的指标。总之,本研究揭示了 miR-505 对 PCa 肿瘤发生的抑制作用,可能通过靶向 NRCAM 发生。NRCAM 和 miR-505 的联合分析可能预测接受根治性前列腺切除术的 PCa 患者的疾病进展。