靶向HMGCS1探讨对宫颈癌细胞线粒体基因表达调控的作用机制OA

Objective:To investigate the mechanism of the regulatory effect of 3-hydroxy-3-methylglutaryl coenzyme A syn-thase 1(HMGCS1)on mitochondrial gene expression in cervical cancer(CC)cells.Methods:Bioinformatics analysis,subcellu-lar structure isolation and localization method,construction of shRNA lentiviral vector and cell transfection,Western blot,real-time fluorescence quantitative PCR,kinetic analysis of RNA synthesis and degradation,and mitochondrial DNA immunoprecipitation-quantitative PCR analysis were utilized to explore the mechanism by which targeting HMGCS1 regulates mi-tochondrial gene expression in CC cells by exploring the mechanism of action of targeting HMGCS1.Results:HMGCS1 expres-sion is up-regulated in CC and predicts poor prognosis;HMGCS1 is mainly differentially expressed in mitochondria;knockdown of HMGCS1 leads to a general down-regulation of the mitochondrial gene expression level in CC cells;knockdown of HMGCS1 may inhibit mitochondrial gene expression by decreasing the level of mitochondrial mRNA synthesis;HMGCS1 may promote the mitochondrial gene transcription of CC cells by regulator binding to mitochondrial DNA(mtDNA)to safeguard the normal tran-scription of mitochondrial genes.Conclusion:HMGCS1 is highly expressed in CC and is associated with poor prognosis.Down-regulated HMGCS1 inhibits mitochondrial gene expression by decreasing the level of mitochondrial mRNA synthesis in CC cells,and HMGCS1 can safeguard the normal transcription of mitochondrial genes by promoting the binding of mitochondrial gene transcriptional regulators to mtDNA in CC cells.Therefore,targeted inhibition of HMGCS1 to regulate mitochondrial gene ex-pression may be a promising new strategy for CC treatment.