TCF21的上调抑制肾上腺皮质癌细胞的迁移。

Upregulation of TCF21 inhibits migration of adrenocortical carcinoma cells.

作者信息

Kremer Jean Lucas, Auricino Thais Barabba, Dos Santos Passaia Bárbara, Lotfi Claudimara Ferini Pacicco

机构信息

Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

出版信息

Discov Oncol. 2021 Jul 23;12(1):23. doi: 10.1007/s12672-021-00417-6.

DOI:10.1007/s12672-021-00417-6

PMID:35201460

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8777580/

Abstract

BACKGROUND

Adrenocortical 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.

METHODS

In 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.

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 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.

CONCLUSIONS

Our results suggest that enhancement of TCF21 expression levels may be a potential strategy to revert invasive abilities in adrenocortical carcinomas.

摘要

背景

肾上腺皮质癌（ACC）是一种罕见且侵袭性强的癌症。我们之前的研究表明，转录因子21（TCF21）在ACC中表达下调，并调节类固醇生成因子1（SF-1）与SF-1 E-box启动子的结合。此外，还发现TCF21是成人癌症总生存期（OS）的一个预测指标。

方法

在本研究中，调查了TCF21表达与肾上腺皮质肿瘤细胞、癌和腺瘤中启动子甲基化状态之间的相关性。检测了TCF21恢复对ACC细胞迁移和侵袭的生物学功能及潜在分子机制。

结果

我们证实了腺瘤和癌细胞中TCF21表达水平与其启动子甲基化之间呈负相关，表明TCF21表达存在表观遗传调控。还通过质粒转染表达TCF21，证明了TCF21的表达抑制ACC细胞系H295R细胞的迁移和侵袭。此外，可能通过Kisspeptin 1（KISS-1）表达、上皮-间质转化（EMT）逆转以及ACC细胞中几种金属蛋白酶的调节，研究了TCF21作为肿瘤抑制因子的功能。