序列相似度60家族成员A在甲状腺乳头状癌中的表达及对细胞增殖的调控作用研究OA

OBJECTIVE To investigate the expression characteristics,biological functions,and potential value as a diagnostic biomarker and therapeutic target of family with sequence similarity 60 member A(FAM60A)in papillary thyroid carcinoma(PTC).METHODS A training cohort was constructed by integrating data from The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)database,comprising 512 PTC tissues and 338 adjacent normal tissues.Datasets from the Gene Expression Omnibus(GEO)database were used as external validation cohorts.Bioinformatics analyses were performed to evaluate the expression characteristics of FAM60A in PTC tissues.Functional assays,including MTT,colony formation,cell cycle,and apoptosis assays,were conducted to assess the effect of FAM60A knockdown on PTC cell proliferation.A subcutaneous xenograft tumor model was established to further validate the in vivo inhibitory effect of FAM60A knockdown on tumor growth.Additionally,the impact of FAM60A knockdown on the expression of relevant genes was examined at both mRNA and protein levels.RESULTS FAM60A was significantly overexpressed in PTC tissues and demonstrated favorable diagnostic value for PTC,with area under the receiver operating characteristic curve(AUC)values of 0.767,0.840,and 0.805 across three cohorts.Knockdown of FAM60A in PTC cells inhibited cell proliferation and colony formation,promoted apoptosis,and altered cell cycle distribution.In vivo experiments in nude mice confirmed that FAM60A knockdown significantly suppressed tumor growth.Mechanistic analyses revealed that FAM60A knockdown led to the differential expression of 1,404 genes and significantly downregulated the expression of CEBPA,Myc,DDIT3,HSPB1,and PTGS2.CONCLUSION FAM60A may participate in the initiation and progression of PTC by regulating the Sin3 histone deacetylase(SIN3-HDAC)transcriptional repression complex,thereby influencing cell cycle progression,proliferation,and differentiation.FAM60A holds promise as a potential diagnostic biomarker and therapeutic target for PTC.