Prostate cancer (PCa) is a heterogeneous tumor that commonly occurs among males worldwide. This study explored the potential role that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) plays in PCa progression, and investigated its mechanism. MCM3AP-AS1 and neuropeptide Y receptor Y1 (NPY1R) expression was determined in PCa cells. The regulatory role of MCM3AP-AS1 in PCa cells was defined using scratch test, Transwell assay, 5-ethynyl-2′-deoxyuridine (EdU) assay, and flow cytometry. Methylation-specific PCR (MSP) was used to test the methylation level of NPY1R. Subsequently, the interaction among MCM3AP-AS1, DNA methyltransferase (DNMT)1/DNMT3 (A/B), and NPY1R was investigated using RNA immunoprecipitation, RNA pull-down, and chromatin immunoprecipitation. Finally, we observed xenograft tumor in nude mice. MCM3AP-AS1 was highly, whereas NPY1R was poorly, expressed in PCa. Lentivirus-mediated overexpression of MCM3AP-AS1 promoted proliferation, invasion, and migration while suppressing apoptosis of PCa cells, whereas opposite trends were detected after inhibition of the mitogen-activated protein kinase (MAPK) pathway. MCM3AP-AS1 promoted methylation of NPY1R promoter via recruitment of DNMT1/DNMT3 (A/B), thereby downregulating NPY1R expression to activate the MAPK pathway. Furthermore, overexpressed MCM3AP-AS1 was observed to facilitate PCa development in vivo, which could be reversed by overexpressed NPY1R. Altogether, MCM3AP-AS1 silencing inhibits PCa progression by disrupting methylation of the NPY1R promoter to inactivate the MAPK pathway.

前列腺癌 (PCa) 是一种异质性肿瘤，常见于全世界的男性中。本研究探讨了长链非编码 RNA MCM3AP 反义 RNA 1 (MCM3AP-AS1) 在 PCa 进展中的潜在作用，并研究了其机制。在 PCa 细胞中测定了 MCM3AP-AS1 和神经肽 Y 受体 Y1 (NPY1R) 的表达。使用划痕试验、Transwell 试验、5-乙炔基-2'-脱氧尿苷 (EdU) 试验和流式细胞术确定 MCM3AP-AS1 在 PCa 细胞中的调节作用。甲基化特异性 PCR (MSP) 用于测试 NPY1R 的甲基化水平。随后，使用 RNA 免疫沉淀、RNA 下拉和染色质免疫沉淀研究了 MCM3AP-AS1、DNA 甲基转移酶 (DNMT)1/DNMT3 (A/B) 和 NPY1R 之间的相互作用。最后，我们在裸鼠中观察到异种移植瘤。MCM3AP-AS1 高，而 NPY1R 表现不佳，在 PCa 中表达。慢病毒介导的 MCM3AP-AS1 过表达促进增殖、侵袭和迁移，同时抑制 PCa 细胞的凋亡，而在抑制丝裂原活化蛋白激酶 (MAPK) 途径后检测到相反的趋势。MCM3AP-AS1 通过募集 DNMT1/DNMT3 (A/B) 促进 NPY1R 启动子的甲基化，从而下调 NPY1R 表达以激活 MAPK 通路。此外，观察到过表达的 MCM3AP-AS1 促进 PCa 发育 MCM3AP-AS1 通过募集 DNMT1/DNMT3 (A/B) 促进 NPY1R 启动子的甲基化，从而下调 NPY1R 表达以激活 MAPK 通路。此外，观察到过表达的 MCM3AP-AS1 促进 PCa 发育 MCM3AP-AS1 通过募集 DNMT1/DNMT3 (A/B) 促进 NPY1R 启动子的甲基化，从而下调 NPY1R 表达以激活 MAPK 通路。此外，观察到过表达的 MCM3AP-AS1 促进 PCa 发育在体内，这可以通过过表达的 NPY1R 来逆转。总之，MCM3AP-AS1 沉默通过破坏 NPY1R 启动子的甲基化使 MAPK 通路失活来抑制 PCa 进展。