ACAA1 Inhibits The Proliferation And Metastasis Of Renal Clear Cell Carcinoma

Background:Clear cell renal cell carcinoma(ccRCC),which originated from renal tubular epithelial cells is the most common histological subtype of renal cell carcinoma(RCC),accounting for about 80% of RCC.The main treatment for ccRCC patients is nephrectomy.And some patients still have tumor recurrence or distant metastasis after surgery.Therefore,to explore the mechanism of development and metastasis of ccRCC will benefit for its early diagnosis and treatment.Some metabolic diseases such as obesity,hyperlipidemia are closely related to the occurrence of RCC,and abnormal expression of key enzymes of fatty acid metabolism are closely related to the proliferation of tumor cells and the prognosis of patients,moreover,their fatty acid metabolites also promote the proliferation and invasion of RCC.In our previous studies,we found that key genes of ketone body metabolism affect the malignant biological behavior of ccRCC cells,and exogenous increase of ketone bodies can inhibit the proliferation of ccRCC.We also found that the fatty acid metabolism gene ACAA1 is down-regulated in ccRCC by bioinformatics.However,there are few studies on fatty acid metabolism and renal clear cell carcinoma.Objective:To explore the transcriptional expression level of ACAA1 gene in ccRCC,and to further investigate the effects of abnormal expression of ACAA1 on the malignant biological behavior of ccRCC and the possible molecular mechanism.Methods:1.Bioinformatics analyzing the relationship between the m RNA transcription levels and clinical parameters of ACAA1 in ccRCC based on the TCGA database,GEO databases and GEPIA.2.Verifying the transcription and expression of ACAA1 in ccRCC c DNA microarray and tissues microarray by real-time RT-PCR and immunohistochemical staining,respectively.3.Establishing the ACAA1 overexpressed ccRCC cell lines,and detecting the biological effects of ACAA1 genes on ccRCC cells by performing proliferation assay,cell migration assay and cell invasion assay.Results:1.The transcription and the expression levels of ACAA1 gene was downregulated in renal clear cell carcinoma.By analyzing base on TCGA database and 24 GEO microarray or RNA-sequencing datasets,,we found that ACAA1 was downregulated in renal clear cells.We further detected the transcription and expression of ACAA1 in ccRCC by real time RT-PCR and immunohistochemistry staining assay and found that ACAA1 was downregulated in ccRCC,which were consistent with bioinformatics anslysis.2.Exogenous overexpression of ACAA1 inhibits the proliferation and invasion of ccRCC By establishing the ACAA1 overexpressed ccRCC cells,we found that ACAA1 inhibits the malignant biological behavior of renal clear cell carcinoma cells,which was validated by proliferation assay,wound healing assay and invasion assay.Conclusion:1.ACAA1 was downregulated in ccRCC.2.ACAA1 can inhibit the malignant biological behavior of renal clear cell carcinoma cells.Overall,ACAA1 could be a candidate tumor suppressor gene in ccRCC.