| Full text | |
| Author(s): |
Passaia, Barbara Dos Santos
;
Kremer, Jean Lucas
;
Villares Fragoso, Maria Candida
;
Pacicco Lotfi, Claudimara Ferini
Total Authors: 4
|
| Document type: | Journal article |
| Source: | NEOPLASMA; v. 69, n. 4, p. 13-pg., 2022-01-01. |
| Abstract | |
Transcription factor 21 (TCF21) directly binds and regulates SF1 mRNA expression in tumor and normal adrenocortical cells, and both are involved in the development and steroidogenesis of the adrenal cortex. TCF21 is a tumor suppressor gene and its expression is reduced in malignant tumors. In adrenocortical tumors, it is less expressed in adrenocortical carcinomas (ACC) than in adrenocortical adenomas (ACA) and normal tissues. However, a comprehensive analysis to identify TCF21 targets has not yet been conducted in any type of cancer. In this study, we performed Chromatin Immunoprecipitation and Sequencing (ChIP-Seq) in an adrenocortical carcinoma cell line (NCI-H295R) overexpressing TCF21, with the aim of identifying TCF21 new targets. The five most frequently identified sequences corresponded to the PRDM7, CNTNAP2, CACNA1B, PTPRN2, and KCNE1B genes. Validation experiments showed that, in NCI-H295R cells, TCF21 negatively regulates the expression of the CACNA1B gene. Recently, it was observed that the N-type calcium channel v2.2 (Cav2.2) encoded by the CACNA1B gene is important in Angiotensin II signal transduction for corticosteroid biosynthesis in NCI-H295R adrenocortical carcinoma cells. Indeed, TCF21 inhibits CACNA1B and Cav2.2 expression in NCI-H295R. In addition, in a cohort of 55 adult patients with adrenocortical tumors, CACNA1B expression was higher in ACC than ACA and was related to poor disease-free survival in ACC patients. These results suggest a mechanism of steroidogenesis control by TCF21 in adrenocortical tumor cells, in addition to the control observed through SF1 inhibition. Importantly, steroid production could impair tumor immunogenicity, contributing to the immune resistance described in adrenal cancer. (AU) | |
| FAPESP's process: | 18/19035-2 - Morphological, functional and molecular study of the cellular differentiation of the adrenal cortex: the role of the SOCS3 gene |
| Grantee: | Claudimara Ferini Pacicco Lotfi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/17285-6 - Study of epigenetic regulation of transcription factor POD-1/TCF21in adrenocortical tumor cell cultures and its role in the cellular migration and invasion |
| Grantee: | Jean Lucas Kremer |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 16/12381-7 - Identification of new targets of transcription factor POD1/TCF21 in human tumor cell cultures |
| Grantee: | Barbara dos Santos Passaia |
| Support Opportunities: | Scholarships in Brazil - Doctorate |