Ji Shuya, Shi Yi, Yang Lin, Zhang Feng, Li Yong, Xu Feng
Department of Oncology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.
Department of General Practice, Shanghai Gonghexin Road Community Health Care Service Center, Shanghai, China.
Front Genet. 2022 Mar 9;13:790621. doi: 10.3389/fgene.2022.790621. eCollection 2022.
Recent studies have shown that the downregulation of miR-145-5p in prostate cancer (PCa) is significantly associated with poor differentiation and prognosis. We aimed to investigate the biological role of miR-145-5p in the neuroendocrine differentiation (NED) of PCa. In this study, TheCancer Genome Atlas was used to identify the association of miR-145-5p with PCa. The functions of miR-145-5p were evaluated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle analysis. We validated changes in cell cycle control by testing the expression of cyclin-related genes by western blot. The luciferase reporter assay was performed to test miR-145-5p-targeting genes and direct transcriptional targets of . The expression of miR-145-5p was found to be significantly downregulated in castration-resistant PCa, and this was correlated with higher Gleason score and prostate-specific antigen. We confirmed these results using PC3 and LNCaP cell lines depicted a gradual decline of miR-145-5p while the cells were cultured under androgen depletion conditions. Moreover, the knockdown of miR-145-5p significantly promoted NED and proliferation of LNCaP cells, whereas overexpression of miR-145-5p significantly inhibited NED and proliferation of LNCaP cells. Mechanistically, we found that was a direct target of miR-145-5p, which regulates might mediate induction of NED and proliferation of LNCaP cells. Furthermore, knockdown of miR-145-5p promoted tumor growth . Our findings suggest that miR-145-5p can inhibit NED and tumor growth by targeting , which regulates the expression of , and that this could be a novel therapeutic strategy for preventing the progression of PCa.
最近的研究表明，前列腺癌（PCa）中miR-145-5p的下调与低分化和预后不良显著相关。我们旨在研究miR-145-5p在PCa神经内分泌分化（NED）中的生物学作用。在本研究中，利用癌症基因组图谱来确定miR-145-5p与PCa的关联。使用细胞计数试剂盒-8（CCK-8）检测法和细胞周期分析来评估miR-145-5p的功能。我们通过蛋白质印迹法检测细胞周期相关基因的表达来验证细胞周期调控的变化。进行荧光素酶报告基因检测以测试miR-145-5p靶向基因和……的直接转录靶点。发现在去势抵抗性PCa中miR-145-5p的表达显著下调，这与更高的Gleason评分和前列腺特异性抗原相关。我们使用PC3和LNCaP细胞系证实了这些结果，在雄激素耗竭条件下培养细胞时，miR-145-5p呈现逐渐下降。此外，敲低miR-145-5p显著促进LNCaP细胞的NED和增殖，而miR-145-5p的过表达显著抑制LNCaP细胞的NED和增殖。从机制上讲，我们发现……是miR-145-5p的直接靶点，其调节……可能介导LNCaP细胞的NED诱导和增殖。此外，敲低miR-145-5p促进肿瘤生长。我们的研究结果表明，miR-145-5p可通过靶向……抑制NED和肿瘤生长，……调节……的表达，这可能是预防PCa进展的一种新的治疗策略。
