LSD1通过MMP13/IL-17途径调控前列腺癌去势抵抗性

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【中图分类号】R737.25 【文献标志码】A

【AbstractObjective：Thisstudyaimed to elucidatetheroleandmolecularmechanismof lysine specificdemethylase1（LSD）in castration-resistant prostatecancer（PCa）.Methods：Bioinformaticsanalysiswas conducted using TheCancer Genome Atlas（TCGA） databasetoexplorethediferentialexpresioandprogosticsignificaneofSDinPCa.Anandrogen-independent（A）celine wasestablishedbysubjectingtheandrogen-dependentLNCapcellineofCatoandrogendeprivation.TheefectsofSDkockdownoncellaacteristicserebseed，nddrgdependentC-3celsretreatedwitteDbior.o thotopictumormodelwasconstructedtoinvestigatetheimpactofLSD1inhibitiononthesensivityofPCatocastrationtherapy.Finally，transcriptoesquening，eal-tiefuoreseneuatiaieCR（PC），Westeblot，ndomatinunopiiatio （ChIP）assays were performed toexplore theunderlying mechanisms.Results ：LSD1wassignificantlyupregulated in TCGA-PCaand castration-resistantPCa.Patients withhighLSD1expressonhadshortersurvivaltimes.TheexpressonofLSDwas higherinLNCapAI cellscomparedtoLNCapcell.LSD1knockdow inhibitedthe malignantehaviorofcelsandincreasedapoptosis.TheLSD1inhibitor suppressed the malignant behavior of PC-3 cells. Inhibition of LSD1 enhanced the sensitivity of PCa to castration therapy. Mechanistically，LSD1 knockdown decreased the expression ofMatrixMetalloproteinase13（MMP13）and inhibited theinterleukin-17 （IL-17）signaling pathway.LSD1 regulated the expression of MMP13bymodulating themethylation level of the H3K9 region in theMMP13 gene promoter.Conclusion：LSD1 controls the expressionofMMP13byregulatingthemethylationlevelof theH3K9regionintheMMP13gnepromoter，therebyinfluencingtheI17sig naling pathway and playing a crucial role inthe progression of castration resistance inprostate cancer.

【Key Wordsllysine-specific demethylase1;prostate cancer;interleukin-17 pathway;matrix metalloproteinase 13

前列腺癌（prostate adenocarcinoma，PCa）作为男性恶性肿瘤中发病率较高的疾病之一，对全球男性健康构成了严重威胁-]。（剩余16589字）