New evidences on the regulation of SF-1 expression by POD1/TCF21 in adrenocortical tumor cells

Abstract

OBJECTIVES:Transcription Factor 21 represses steroidogenic factor 1, a nuclear receptor required for gonadal development, sex determination and the regulation of adrenogonadal steroidogenesis. The aim of this study was to investigate whether silencing or overexpression of the gene Transcription Factor 21 could modulate the gene and protein expression of steroidogenic factor 1 in adrenocortical tumors.METHODS:We analyzed the gene expression of steroidogenic factor 1 using qPCR after silencing endogenous Transcription Factor 21 in pediatric adrenal adenoma-T7 cells through small interfering RNA. In addition, using overexpression of Transcription Factor 21 in human adrenocortical carcinoma cells, we analyzed the protein expression of steroidogenic factor 1 using Western blotting.RESULTS:Transcription Factor 21 knockdown increased the mRNA expression of steroidogenic factor 1 by 5.97-fold in pediatric adrenal adenoma-T7 cells. Additionally, Transcription Factor 21 overexpression inhibited the protein expression of steroidogenic factor 1 by 0.41-fold and 0.64-fold in two different adult adrenocortical carcinoma cell cultures, H295R and T36, respectively.CONCLUSIONS:Transcription Factor 21 is downregulated in adrenocortical carcinoma cells. Taken together, these findings support the hypothesis that Transcription Factor 21 is a regulator of steroidogenic factor 1 and is a tumor suppressor gene in pediatric and adult adrenocortical tumors.

Role of the bHLH transcription factor TCF21 in development and tumorigenesis

“…Increased expression of TCF21 in H295R and ACC-T36 cells and in primary culture of rat ACC decreased SF-1/NR5A1 and steroidogenic enzyme StAR expression ( 65 , 84 ). In cultures of ACA cells obtained from pediatric tumor fragments, ACA-T7 cells, TCF21 silencing by small interfering RNA led to an increase in SF1 mRNA expression ( 85 ). Although SF-1 regulates steroid production, it is also related to adrenocortical cell proliferation ( 86 , 87 ).…”

Construction of a risk signature for adrenocortical carcinoma using immune-related genes

“…Among all differentially expressed TFs in ACC patients, centromere protein A (CENPA) (46), E2F transcription factor 1 (E2F1) (47) and forkhead box M1 (FOMX1) (48) showed upregulated expression that was involved in ACC progression and predicted a poor prognosis. In contrast, downregulation of transcription factor 21 (TCF21) expression resulted in the accumulation of secreted glucocorticoids and accelerated proliferation of ACC cells, indicating that TCF21 is a potential prognostic marker in ACC (49)(50)(51). Additionally, a previous study reported that Activin could induce x-zone apoptosis to inhibit ACC cell growth induced by SMAD family member 2 (Smad2) (52).…”