Overexpression of BHLHE41, correlated with DNA hypomethylation in 3′UTR region, promotes the growth of human clear cell renal cell carcinoma

Basic helix-loop-helix family member e41 (BHLHE41) serves an important role in regulating cell differentiation, circadian rhythms and the response to hypoxia. However, the roles of BHLHE41 in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of the present study was to analyze the expression of BHLHE41 in ccRCC and investigate the effect of downregulated BHLHE41 on the growth and migration of ccRCC cells. The expression of BHLHE41 in ccRCC was demonstrated to be significantly increased in gene expression microarray datasets and RNA sequencing data. Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that BHLHE41 expression in fresh ccRCC tissues was increased, compared with than their adjacent non-tumorous controls. BHLHE41 knockdown significantly reduced cell proliferation and migration of A498 and CAKI-1 cells. For the investigation of the molecules mediated by BHLHE41, immunoblotting analyses revealed that phosphorylation of p70S6K and protein levels of E-cadherin were reduced. Additionally, a lower frequency methylation was determined in the BHLHE41 3′-untranslated region through The Cancer Genome Atlas dataset analysis for the first time. These observations demonstrated that BHLHE41 could be a biomarker and an oncogene for ccRCC.