Genome-wide analysis of DNA methylation identifies the apoptosis-related gene UQCRH in renal cancer

Abstract

Background DNA hypermethylation is frequently observed in clear cell renal cell carcinoma (ccRCC) and correlates with poor clinical outcomes. However, the detailed function is not fully uncovered. Methods A target for DNA methyltransferases (DNMTs) was explored in ccRCC cells. Highly malignant derivatives of human ccRCC cells were established via serial orthotopic inoculation in mice. Then, DNA methylated sites were genome-widely analyzed using methylation array in reference to RNA-sequencing data. Results We found that DNMT3B upregulation contributes to renal cancer progression and identified the ubiquinol cytochrome c reductase hinge protein (UQCRH) as a methylation target in advanced ccRCC. The expression of UQCRH in human ccRCC tissues was lower than that in normal adjacent tissues. Furthermore, its silencing attenuated cytochrome c release in response to apoptotic stimuli, resulting in enhanced primary tumor formation in vivo. Moreover, DNA demethylation enhanced the therapeutic efficiency of the mammalian target of rapamycin (mTOR) inhibitor everolimus in vivo. Conclusions These findings suggest that the DNMT3B-induced UQCRH methylation may contribute to renal cancer progression and that DNMT inhibitors exhibit potential clinical significance for ccRCC treatment.

Integrative Genome-Wide DNA Methylome and Transcriptome Analysis of Ovaries from Hu Sheep with High and Low Prolific

“…DNA methylation is an epigenetic modification that regulates gene expression and serves as a key regulator of development (Fan et al, 2020;Yang et al, 2021), differentiation (Khavari et al, 2010), and other processes (Miyakuni et al, 2021). Recent studies have shifted their focus toward how DNA methylation regulates pubertal onset (Lomniczi et al, 2015;Yang et al, 2016;Yuan et al, 2019), estrus (An et al, 2018;Zhou et al, 2018), ovary (Wang et al, 2014;Yu et al, 2015;Sagvekar et al, 2019), oocyte (Mattern et al, 2017;Wei et al, 2019), and embryo development (Salilew-Wondim et al, 2015;Canovas et al, 2017), and reproductive diseases (Vazquez-Martinez et al, 2019;Cao et al, 2021;Zhong et al, 2021).…”