CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma

Abstract

BackgroundCytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC.MethodsExpression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses.ResultsFirst, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples.ConclusionsCYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC.

lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1 /Suz12 Complex in the CNS

“…lncOL1 -Suz12 target gene sets (genes upregulated in lncOL1 null cells with promoters occupied by Suz12) are associated with cell growth and proliferation, and their expression is enriched in OPCs (Figure 7J). These include Igf2 , which encodes insulinlike growth factor 2 that promotes OPC growth and proliferation (Frederick and Wood, 2004; Zhang et al, 2010), H19 , which is an imprinted lncRNA that promotes progenitor cell proliferation (Ratajczak, 2012), and Cyp1b1 , which encodes the cytochrome P450 family protein that enhances cell proliferation and tumorigenesis (Mitsui et al, 2015) (Figure 7K). These genes are highly expressed in OPCs, but strongly repressed during OL maturation (Figures S6F and S6G) (Dugas et al, 2006; Zhang et al, 2014), suggesting that their expression maintains OPCs in the precursor state.…”

Identification of differentially expressed genes in hepatocellular carcinoma by integrated bioinformatic analysis

“…Recently, an increasing number of studies have shown that CDC20 is a carcinogenic factor that is widely regulated in a variety of human malignancies, including lung cancer, kidney cancer and prostate cancer. Furthermore, CDC20 is closely related topoor prognosis of a tumor [35–37].…”

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

“…Melatonin also promotes cancer cell apoptosis by inducing cell cycle arrest . Another phenomenon worth noting is that CYP1B1 overexpression itself could enhance proliferation, migration, and invasion of tumor cells in prostate cancer and kidney cancer . Therefore, inferior survival in the low‐Index‐III subgroup might also be attributable to overexpression of CYP1B1 in some cancer types; further experimental studies are needed to reveal the underlying mechanism in different cancer types in this note.…”

“…30 Another phenomenon worth noting is that CYP1B1 overexpression itself could enhance proliferation, migration, and invasion of tumor cells in prostate cancer and kidney cancer. 31,32 Therefore, inferior survival in the low-Index-III subgroup might also be attributable to overexpression of CYP1B1 in some cancer types; further experimental studies are needed to reveal the underlying mechanism in different cancer types in this note. The valid associations between melatonin and risk of death have facilitated randomized controlled clinical trials (RCTs) investigating the therapeutic roles of melatonin in improving survival outcomes and tumor responses.…”