The Function And Mechanism Of CircPSD3 In Clear Cell Renal Cell Carcinoma

Objective:Clear cell renal cell carcinoma(cc RCC)is a common malignant tumor of the urinary system.Metastatic cc RCC has a poor prognosis,and there is still a lack of effective diagnostic markers and treatments.circular RNA(circ RNA)is a new class of non-coding RNA that play an important regulatory role in the occurrence and development of tumors.However,the role of circ RNA in cc RCC has not been fully elucidated.The purpose of this paper is to elucidate the role of circ RNA in the occurrence and development of cc RCC.Method:1.circ PSD3 was screened out through the circ RNA expression profile GSE100186 in the GEO database and the sequencing data of our research group,and then the expression of circ PSD3 in 81 pairs of human cc RCC tissues and paired adjacent tissues was analyzed by real-time PCR.and clinicopathological characteristics.2.The circ PSD3 stable overexpression cell model was constructed by lentivirus,and the proliferation,migration,and invasion functions of circ PSD3 in cc RCC cells were evaluated by CCK-8,transwell,and scratch wound healing assays,respectively.The effects of circ PSD3 on tumor growth and metastasis in vivo were examined by subcutaneously transplanted tumors in nude mice and lung metastasis models by tail vein injection.3.The relationship between circ PSD3 and micro RNA 25-3p(mi R-25-3p)was analyzed by bioinformatics analysis,RNA pull down,FISH,and luciferase reporter gene assay.4.To investigate whether there is an interaction between circ PSD3 and mi R-25-3p in renal clear cell carcinoma cells and changes in cell function by using CCK-8,transwell,and scratch wound healing assays.5.F-box and WD repeat domain containing 7(FBXW7)was identified as mi R-25-3p target genes by bioinformatics analysis and luciferase reporter gene assay.The effects of circ PSD3 and mi R-25-3p on FBXW7 expression and EMT in cc RCC cells by q RT-PCR and western blot analysis Results:1.Bioinformatics analysis found a total of 14 significantly differentially expressed circ RNA in the circ RNA expression profile GSE100186 of GEO database and the sequencing data of our group,among which has＿circ＿0002111(circ PSD3)was significantly differentially expressed in both cohorts.2.q RT-PCR results showed that the expression of circ PSD3 was down-regulated in cc RCC tissues and the low expression of circ PSD3 was associated with tumor metastasis in cc RCC patients.3.After overexpression of circ PSD3 in ACHN and Caki-1 cells,the results of in vitro and in vivo experiments showed that overexpression of circ PSD3 inhibited cell and tumor proliferation,migration,and epithelial-mesenchymal transition(EMT).4.Overexpression of circ PSD3 inhibited proliferation,migration,and invasion in clear cell renal cell carcinoma ACHN and Caki-1 cells,while mi R-25-3p rescued the effects of circ PSD3 on cell proliferation,migration,and invasion.5.Overexpression of circ PSD3 as a competitive endogenous RNA of mi R-25-3p promotes the expression of FBXW7 m RNA and protein,thereby inhibiting the EMT-like phenotype of cc RCC cells.Conclusion:1.Bioinformatics and q RT-PCR results showed that the expression of circ PSD3 was downregulated in cc RCC tissues and the low expression of circ PSD3 was associated with tumor metastasis in cc RCC patients.2.circ PSD3 can inhibit tumor invasion and metastasis by inhibiting mi R-25-3p/FBXW7-EMT axis.3.As a "tumor suppressor gene",circ PSD3 is expected to be a potential target for the diagnosis and treatment of cc RCC.