Objective To investigate the effect of promoter methylation of axis inhibition protein 2(AXIN2)gene on gene transcription in cutaneous basal cell carcinoma(BCC)and the mechanismof miR-214-5p sregulation of Axis inhibition protein 2(AXIN2)methylation rate by targeting DNA methyltrans-ferase1(DNMT1).Methods From January 2022 to June 2023,102 BCC patients'sample and baseline da-ta who were treated in Guangzhou Institute of Dermatology were collected as the study objects.The meth-ylation rate of AXIN2 gene promoter region was quantitatively determined by pyrosequencing.real-time quantitative(PCR)was used to detect AXIN2,DNMT1 mRNA and miR-214-5p expression levels.The basal cell carcinoma A431 cells were transfected with miR-214-5p mimic,inhibitor and negative control mimic NC,respectively.The mRNA expression level of DNMT1 gene and the methylation rate of AXIN2 gene were detected 48 h later.Results The methylation rate of AXIN2 gene in BCC was significantly higher than that in paracanceral normal tissues(t=5.128,P＜0.001),and the mRNA relative expression level of AXIN2 gene was significantly lower than that in paracanceral normal tissues(t=7.826,P＜0.001).The mRNA expression level of DNMT1 gene was significantly higher than that of paracancerous normal tissues(t=4.838,P＜0.001),and the expression level of miR-214-5p was significantly lower than that of paracancerous normal tissues(t=5.426,P＜0.001).The methylation rate of AXIN2 gene in BCC cancer tissue was negatively correlated with its mRNA expression level(r=-0.793,P＜0.001),and the mRNA level of DNMT1 gene was positively correlated with the methylation rate of AXIN2 gene(r=0.814,P＜0.001).The expression level of miR-214-5p was negatively correlated with the mRNA level of DNMT1 gene(r=-0.747,P＜0.001).The results of double luciferase reporter gene experiment con-firmed that DNMT1 was the target gene of miR-214-5p.After transfection,the mRNA levels of DNMT1 gene and the methylation rate of AXIN2 gene in mimic were significantly decreased compared with those of mimic NC,inhibitor and inhibitor NC(P＜0.001).The mRNA level of DNMT1 gene and the methyla-tion rate of AXIN2 gene in inhibitor were significantly increased compared with the other three(P＜0.001).Conclusion miR-214-5p can affect the DNA methylation rate of AXIN2 gene by regulating the ex-pression of downstream target protein DNMT1,regulate the expression level of AXIN2 gene and partici-pate in the pathogenesis of skin basal cell carcinoma.
basal cell carcinomamiR-214-5pDNA methyltransferase1axial inhibitory protein2promot-er region methylation
维普
万方数据
