Abstract
Patients with renal cell carcinoma (RCC) usually develop drug resistance and have poor prognosis owing to its insensitive property. However, the underlying mechanisms of RCC are still unclear. We implemented an integrative analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets. Three genes (CRHBP, RAB25 and PSAT1) were found to be potential biomarkers in ccRCC and validated by four independent cohorts. Then, ccRCC patients with a decreased expression of CRHBP in tumor tissues had significantly poor survival by TCGA ccRCC datasets and verified by clinical samples as well as RCC cell lines. Overexpression of CRHBP suppressed cell proliferation, migration, invasion as well as apoptosis in vitro and in vivo. Moreover, the results of western blot analysis showed the effects of CRHBP via upregulating NF-κB and p53-mediated mitochondria apoptotic pathway. Our results suggested that CRHBP may be an effective target to treat ccRCC patients.
Highlights
Renal cell carcinoma (RCC), the third most common malignancy of the urinary system, is the sixth most frequently diagnosed malignant neoplasms in men and tenth in women accounting for 4% of all cancers [1, 2]
Recent studies showed that corticotropin releasing factor binding protein (CRHBP) expression is linked with high α-fetoprotein level in patients with hepatocellular carcinoma (HCC), and HCC patients with low CRHBP expression have poor overall survival rate [7]
We revealed that the expression of CRHBP is aberrantly decreased in ccRCC samples and cell lines, and positively associated with overall survival rate of patients
Summary
Renal cell carcinoma (RCC), the third most common malignancy of the urinary system, is the sixth most frequently diagnosed malignant neoplasms in men and tenth in women accounting for 4% of all cancers [1, 2]. Clear renal cell carcinoma (ccRCC), one of the most frequently histologic subtypes of RCC, derives from the renal parenchyma urinary tubule epithelial cell representing ~70–85% of all RCC diagnoses [3]. Due to unconspicuous symptoms in early stage of ccRCCs, about 30% patients have localized or. These authors contributed : Pengcheng Luo, Fan Cheng. According to the nextgeneration sequencing technology, numerous differentially expressed genes (DEGs) have been served as biomarkers for ccRCC pathogenesis or potential therapeutic targets. Hypermethylation level of CRHBP was significantly negative with mRNA expression based on methylated microarray, and alteration of methylation level could affect ccRCC cell lines migration and invasion [8]. Few potential mechanistic researches reveal how CRHBP affects the progress and metastasis of ccRCC
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