The Role Of MiR-200c In Abnormal Proliferation Of Human Pulmonary Artery Smooth Muscle Cells

Background:Pulmonary hypertension(PH)is a progressive and devastating disease characterized by excessive pulmonary vasoconstriction and abnormal vascular wall remodeling.The latter is related with imbalanced proliferation and apoptosis of pulmonary artery smooth muscle cells(PASMCs).Although PH pathology has been extensively investigated,more detailed molecular and cellular mechanisms involved in regulating pulmonary vascular proliferation remain largely obscure.microRNAs(miRNAs)are noncoding RNAs that miRNA plays a significant role in cell transcription and other processes.Zinc finger E-box binding homeobox1(ZEB-1)is a transcription factor that plays crucial roles in the epithelial to mesenchymal transition of cancer cell.Abnormal miRNA expression plays an important role in vascular cell remodeling process in PH.mi RNAs might mediate cell proliferation and/or apoptosis of PASMCs.miR-200 c belongs to the mi R-200 family,an important target in cancer development.miR-200 c is also an important factor in inhibiting differentiation and proliferation of various cells,as well as inducing cell apoptosis.These studies have demonstrated that miR-200 c played a crucial role in the proliferation of PASMCs.However,the regulatory and functional roles of miR-200 c in ET-1 induced PASMCs have not been comprehensively investigated.In this study,we aim to identify the target genes of miR-200 c and demonstrate how miR-200 c works in PASMCs.Objective:To study the role of miR-200 c in the abnormal proliferation of human pulmonary artery smooth muscle cells(PASMCs)and its potential mechanism.Methods:Pulmonary arterial smooth muscle cells were cultured and stimulated with endothelin(ET-1)to detect miR-200 c expression.Interfere with the expression ofmiR-200 c in PASMCs,make them over-expressed and low-expressed,and detect cell proliferation and apoptosis,zinc finger transcription inhibitors-1(ZEB-1)changes in mRNA levels and protein expression levels.Result : The expression of miR-200 c in PASMCs was significantly upwnregulated after endothelin(ET-1)stimulation.The overexpression of miR-200 c significantly decreased the percentage of apoptotic cells,while the percentage of apoptotic cells was significantly increased after interference with miR-200 c.After miR-200 c was expressed,the mRNA and protein expression level of ZEB-1decreased.However,the expression level of ZEB-1 gene was significantly increased after interfering with miR-200 c.Conclusions:There is a significant correlation between miR-200 c and proliferation of PASMCs.In the process of proliferation of PASMCs,miR-200 c acts as a facilitating factor.The abnormal increase of PASMCs may cause the proliferation of PASMCs,leading to the occurrence of PAH.ZEB-1 may be involved in the proliferation/apoptosis regulation of PASMCs as a target of miR-200 c.