Knockdown of MCM3AP-AS1 Inhibits Proliferation, Invasion and Migration of Prostate Cancer Cells via DNMT1/DNMT3 (A/B) Methylation-Mediated Upregulation of NPY1R

Abstract Prostate cancer (PCa) is a heterogeneous tumor that commonly occurs among males worldwide. This study explored potential role long non-coding RNA 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 of MCM3AP-AS1 in PCa cells was defined using scratch test, Transwell assay, 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 while NPY1R was poorly expressed in PCa. Lentivirus-mediated overexpression of MCM3AP-AS1 promoted proliferation, invasion and migration while suppressing apoptosis of PCa cells, while opposite trends were detected after inhibition of MAPK pathway. MCM3AP-AS1 promoted methylation of NPY1R promoter via recruitment of DNMT1/DNMT3 (A/B), thereby downregulating NPY1R expression to activate the mitogen-activated protein kinase (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.