Function And Mechanism Of RNA M5C Modified Long Non-coding RNA MAFG-AS1 In Prostate Cancer

Background and objectiveProstate cancer(PCa)is a common male malignancy and a highly heterogeneous disease.At present,epigenetic regulation is considered to be an important cause of disease heterogeneity.In terms of epigenetic regulation,it has been confirmed that 5-methylcytosine(m5C)modified long non-coding RNA(lndRNA)has regulatory effects on a variety of solid tumors.By analyzing the transcripome data of PCa patients in the TCGA database,this study screened m5C-related lndRNA that were closely related to biochemical recurrence of PCa(BCR),studies the expression changes of m5C related lndRNA on the cellular biological activity of PCa,and explores their pathways to exert biological functions within cells.MethodDownload PCa patient transcriptome data from TCGA and GEO databases.The m5C-related lndRNA closely related to BCR were screened using bioinformatics analysis technology,and the m5C-lnc score BCR prediction model was constructed and verified.Competitive endogenous RNA(ceRNA)network and lncRNA-protein interaction network were established to perform functional enrichment analysis of m5C related lncRNAs.The knockout phenotype of MAFG-AS1 was constructed and its effect on the function of prostate cancer cells was studied by CCK8,Transwell and clonal colony formation tests.The function of RNA-binding protein ALYREF in PCa was studied by RNA-seq and RIP-seq techniques.The effect of ALYREF on tumor growth was studied by tumor inhibition experiment in vivo.The interaction between MAFG-AS1 and ALYREF was studied by CHIRP,RIP and WB experiments.Results17 m5C modified lncRNAs,which were closely related to BCR,were screened to construct the m5C lnc score prediction model.Patients were grouped at risk using the model,and KM survival analysis showed a statistically significant difference in the rate of no biochemical recurrence between the high and low risk groups.ROC curve and DCA curve analysis showed that the prediction model was more accurate.Among the 17 lncRNAs,9 participated in the ceRNA network,and 8 had protein interaction.Functional enrichment analysis of m5C related lncRNAs showed that they were mainly involved in heterocyclic metabolism,base-containing compound metabolism and RNA transport pathway.Inhibiting the expression of MAFG-AS1 in prostate cancer cells can reduce the proliferation and migration of tumor cells.Inhibition of ALYREF expression could significantly inhibit tumor growth in nude mice.MAFG-AS1 can bind to ALYREF,and the binding site is mainly between 160-380bp.ConclusionThe m5C-lnc scoring model can be used to accurately stratify the risk of biochemical recurrence in prostate cancer patients.Inhibition of m5C associated lncRNA MAFG-AS1 expression can reduce the proliferation and migration of prostate cancer cells.m5C related lncRNA MAFG-AS1 can bind to the m5C modified RNA-binding protein ALYREF,which may exert its biological function through lncRNA-protein interaction.