右江医学2026，Vol.54Issue(7)：633-640,8.DOI:10.3969/j.issn.1003-1383.2026.07.002
miRNAs调控JAK2/STAT3信号通路激活在纳米二氧化钛致卵巢颗粒细胞凋亡中的作用及机制研究
Study on the role and mechanism of miRNAs in the regulation of the activation of JAK2/STAT3 signaling pathway in titanium dioxide nanoparticle-induced apoptosis of ovarian granulosa cells
摘要
Abstract
Objective To investigate the effect and potential molecular mechanism of titanium dioxide nanoparticles(TiO2NP)in inducing apoptosis of ovarian granulosa cells,so as to clarify the regulatory effect of differentially expressed microRNA(miRNA)on the JAK2/STAT3 signaling pathway.Methods Human ovarian granulosa cell line COV434 was used as research object and treated with 0,5,10,and 20 μg/mL TiO2NP for 24 h,respectively.Cell viability was assessed by MTT assay,and the apoptosis rate was measured by flow cytometry with Annexin V/PI double staining.Western blot was used to detect the expression levels of apoptosis-related proteins cleaved Caspase-3/6/9 and key molecules of the JAK2/STAT3 signaling pathway.Differentially expressed miRNAs induced by TiO2NP were screened by miRNA expression microar-ray,followed by KEGG pathway enrichment analysis and construction of the miRNA-mRNA regulatory network through bioin-formatics analysis.RT-qPCR was performed to verify the mRNA expression levels of core pathway molecules.Results TiO2NP decreased the viability of COV434 cells in a dose-dependent manner,with cell viability dropping to 43.27％in the 20 μg/mL group.Simultaneously,TiO2NP increased the apoptosis rate and upregulated the protein expression of cleaved Caspase-3/6/9 in a dose-dependent manner(all P<0.05).A total of 10 differentially expressed miRNAs(5 upregulated and 5 downregulated)were screened by miRNA expression profiling microarray.KEGG enrichment analysis revealed the JAK2/STAT3 signaling pathway as the core regulatory pathway,and the miRNA-mRNA network suggested JAK2,STAT3,SOCS4,SOCS5,SOCS6,and PTPN6 as core regulatory targets.RT-qPCR and Western blot verification demonstrated that TiO2NP could dose-dependently downregulate the mRNA and protein expression levels of JAK2 and STAT3,and upregulate the mRNA and protein expression of SOCS4,SOCS5,SOCS6,and PTPN6(all P<0.05).Conclusion TiO2NP may inhib-it JAK2/STAT3 pathway activation by regulating the miRNA expression profile,thereby inducing apoptosis.This study pro-vides experimental evidence for the screening and prevention of biological markers of reproductive toxicity of nano-titanium di-oxide.关键词
纳米二氧化钛颗粒/卵巢颗粒细胞/细胞凋亡/微小RNA/JAK2/STAT3信号通路Key words
titanium dioxide nanoparticles(TiO2NP)/ovarian granulosa cells/apoptosis/microRNA(miRNA)/JAK2/STAT3 signaling pathway分类
医药卫生引用本文复制引用
高国栋,袁恺晨,林梦麒,向心平,黄林凤..miRNAs调控JAK2/STAT3信号通路激活在纳米二氧化钛致卵巢颗粒细胞凋亡中的作用及机制研究[J].右江医学,2026,54(7):633-640,8.基金项目
江西省自然科学基金(20212BAB206070) （20212BAB206070）
江西省卫健委科技计划项目(202410427) （202410427）
