N-type calcium channel v2.2 is a target of TCF21 in adrenocortical carcinomas

Autor(es)

Passaia, Barbara Dos Santos ; Kremer, Jean Lucas ; Villares Fragoso, Maria Candida ; Pacicco Lotfi, Claudimara Ferini

• Tipo de documento: Artigo Científico
• Fonte: NEOPLASMA; v. 69, n. 4, p. 13-pg., 2022-01-01.

Resumo

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)

• Processo FAPESP: 18/19035-2 - Estudo morfológico, funcional e molecular da diferenciação celular do córtex adrenal: o papel do gene SOCS3
• Beneficiário: Claudimara Ferini Pacicco Lotfi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/17285-6 - Análise da regulação epigenética do fator de transcrição POD1/TCF21 em culturas de células de tumores adrenocorticais, e seu papel na migração e invasão celular.
• Beneficiário: Jean Lucas Kremer
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/12381-7 - Identificação de novos alvos do fator de transcrição POD1/TCF21 em culturas de células de tumores humanos
• Beneficiário: Barbara dos Santos Passaia
• Modalidade de apoio: Bolsas no Brasil - Doutorado