Investigation Of Long Noncoding RNA MRCCAT1 Promoting Metastasis Of Clear Cell Renal Cell Carcinoma Via Inhibiting NPR3 And Activating P38-MAPK Signaling

Background and Objective Renal cell carcinoma accounts for 3% of adult tumors,accounting for about 85% of malignant renal tumors.the third urinary tract tumors,following Prostate cancer and bladder cancer,has very high mortality,about 40%.Clear cell carcinoma is the most common subtype of renal cell carcinoma,accounting for 70-80% of all renal cell carcinomas.In addition to surgical resection,renal cell carcinoma is less sensitive to chemotherapy and radiotherapy.At present,due to lack of effective biomarkers for early diagnosis and late follow-up,some tumors have been found to be late or metastatic,and the prognosis is poor.The 5 year survival rate is less than 25%.Therefore,strengthening the research of metastatic renal cell carcinoma is very urgent and important for finding biomarkers.At present,due to the rapid development of genome sequencing technology,RNA transcripts was found to play an important role in the development of kidney disease,especially lncRNA(long noncoding non RNA)has been discovered a previously unrecognized functional regulation in the process of chromosome modifications and gene expression.Based on the latest research progress of tumor molecular biology,To reveal the function of lncRNA in the pathogenesis and progression of tumor,one of the best methods is to analyze and study the expression profile of LncRNA.objective of this study is to assess the effects of MRCCAT1 metastasis of clear cell renal cell carcinoma(ccRCC).Methods: The expression of MRCCAT1 in human ccRCC samples was determined on a gene expression microarray.MRCCAT1 knockdown and overexpression studies were performed in ccRCC cells to evaluate changes in cell proliferation,migration and invasion.A metastasis model was used to examine the metastatic capability of ccRCC cells on MRCCAT1 suppression.Results: we identified a novel lncRNA associated with metastatic ccRCC(MRCCAT1)by lncRNA microarray.MRCCAT1 was highly expressed in metastatic ccRCC tissues and was closely associated with ccRCC metastasis and poor prognosis.Multivariate Cox regression analysis revealed that MRCCAT1 was an independent prognostic factor in ccRCC patients.MRCCAT1 overexpression promoted cell proliferation,migration and invasion,while MRCCAT1 knockdown expression repressed these properties both in vitro and in vivo.Mechanistic studies further revealed that MRCCAT1 promote ccRCC metastasis by negatively regulating NPR3 expression and then activating adenylyl cyclase and P-P38 MAPK signaling pathway.Conclusions: MRCCAT1 is a critical lncRNA that primarily serves as a prognostic factor for ccRCC patient survival.MRCCAT1 could serve as a biomarker for identifying metastatic ccRCC and as a therapeutic target for ccRCC patients.