Role Of MiR-125b In Regulating The Progression Of RCC By Targeting VDR

Background: Renal cell carcinoma(RCC)accounts for approximately 3% of all human cancers and is one of the most lethal urological malignancies.It is estimated that there were 73,820 new cases diagnosed and 14,770 deaths in 2019 in United States.Therefore,it is urgent need to study the molecular mechanism of the occurrence and development of RCC,which may provide a new treatment method for RCC.We previously found that vitamin D receptor(VDR)expression was decreased in RCC compared with normal kidney tissues,which correlated with pathological type of RCC.We further demonstrated that VDR could suppress proliferation and metastasis in RCC cell lines.Our found that miR-125 b could potentially targeting VDR by online website.However,there are currently no studies regarding the correlation between miR-125 b expression and VDR in RCC.The aim of this study is to investigate the expression of miR-125 b and VDR in the RCC,and assess the possible association between them.Then,to elucidate whether miR-125 b could regulate the expression of VDR and affect proliferation and metastasis in RCCMartial and Methods: The expression of miR-125 b was detected by quantitative Real-Time Polymerase Chain Reaction(qRT-PCR)in RCC cell lines and 293 T cell.ACHN cell of miR-125 b mimic and 786-O cell of miR-125 b inhibitor model were constructed by transient transfection.Several functional experiments were employed to measure the influence of miR-125 b in cell proliferation,apoptosis,migration and invasion by MTT assay,flow cytometry assay and transwell assay.The miR-125 and VDR relationship was verified using luciferase assays,and the expression of them were also examined in primary tumor and normal peritumoral kidney tissues in 20 clear cell RCC(ccRCC)samples.Results: MiR-125 b significantly upregulated in RCC cell lines,and miR-125 b expression in 786-O was observed higher compared to ACHN cells.MiR-125 b mimic significantly promote migration and invasion,and induce apoptosis in ACHN cell lines,while miR-125 b inhibitors inhibited migration and invasion in 786-O cells.Overexpression of miR-125 b could decrease VDR expression via targeting VDR.Expression of miR-125 b mRNA significantly increased in ccRCC than that in normal adjacent tissues,and the expression of miR-125 b mRNA negative correlated with that of VDR was also detected.Conclusions: Overexpression of miR-125 b could decrease the expression of VDR and promoted migration and invasion in RCC cell,and there was a negative correlation between miR-125 b and VDR expression in ccRCC.These finding may contribute to the development of new gene therapy strategies for RCC.