Abstract
BackgroundAdrenocortical carcinomas (ACC) are rare and aggressive cancer. Our previous study has revealed that the transcription factor 21, TCF21, is downregulated in ACC and regulates steroidogenic factor 1 (SF-1) binding to the SF-1 E-box promoter. In addition, it could be found that TCF21 is a predictor of overall survival (OS) in adult carcinomas.MethodsIn this study, it was investigated the correlation between TCF21 expression and the promoter methylation status in adrenocortical tumor cells, carcinomas and adenoma. The biological function and potential molecular mechanism of TCF21 restoration in migration and invasion of ACC cells was examined.ResultsWe could be demonstrated a negative correlation between the level of TCF21 expression and methylation of its promoter in adenoma and carcinoma cells indicating the epigenetic control of TCF21 expression. It was also demonstrated that the expression of TCF21 inhibits migration and invasion in the ACC cell line, H295R cells, using plasmid transfection to express TCF21. Furthermore, it could be investigated the TCF21 function as tumor suppressor probably through Kisspeptin 1 (KISS-1) expression and epithelial–mesenchymal transition (EMT) reversion, as well as the modulation of several metalloproteinases in ACC cells.ConclusionsOur results suggest that enhancement of TCF21 expression levels may be a potential strategy to revert invasive abilities in adrenocortical carcinomas.
Highlights
Adrenocortical tumors are usually incidentally diagnosed in 6–7% of the population [1]
Analysis of Transcription factor 21 (TCF21) expression in different adrenocortical tumor cell cultures (Fig. 1A) showed lower mRNA expression of TCF21 in human Adrenocortical carcinomas (ACC) cells; H295R cells and ACC-T36 cells when compared to cell culture from pediatric adenoma, ACAPedT7 and human normal adrenal pool (NA), which was used as reference
To confirm the regulation of TCF21 by promoter methylation, H295R cells were treated with demethylating agent 5-aza-2-deoxycytidine (5-aza). 100 μM of 5-aza for 48 h increased the relative expression of TCF21 mRNA level reversing the hypermethylation condition of the TCF21 promoter (Figure 1S)
Summary
Adrenocortical tumors are usually incidentally diagnosed in 6–7% of the population [1]. Methods In this study, it was investigated the correlation between TCF21 expression and the promoter methylation status in adrenocortical tumor cells, carcinomas and adenoma. Results We could be demonstrated a negative correlation between the level of TCF21 expression and methylation of its promoter in adenoma and carcinoma cells indicating the epigenetic control of TCF21 expression. It was demonstrated that the expression of TCF21 inhibits migration and invasion in the ACC cell line, H295R cells, using plasmid transfection to express TCF21 It could be investigated the TCF21 function as tumor suppressor probably through Kisspeptin 1 (KISS-1) expression and epithelial–mesenchymal transition (EMT) reversion, as well as the modulation of several metalloproteinases in ACC cells. Conclusions Our results suggest that enhancement of TCF21 expression levels may be a potential strategy to revert invasive abilities in adrenocortical carcinomas
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