Glucocorticoid promotes metastasis of colorectal cancer via co-regulation of glucocorticoid receptor and TET2

文献类型： 外文期刊

第一作者： Song, Yanwei

作者： Song, Yanwei;Ren, Shuqiang;Wu, Shumei;Hu, Chenghao;Feng, Siting;Chen, Xinyu;Liu, Weidong;Tu, Rui;Gao, Fei;Gao, Fei

作者机构：

关键词： colorectal cancer; drug repositioning; glucocorticoid receptor; TET2

期刊名称：INTERNATIONAL JOURNAL OF CANCER （ 影响因子：4.7； 五年影响因子：5.9 ）

ISSN： 0020-7136

年卷期： 2025 年 156 卷 8 期

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收录情况： SCI

摘要： Glucocorticoids (GCs), commonly used for anti-inflammatory and cancer treatments, have been linked to the promotion of cancer metastasis. Yet, the molecular mechanisms behind this potential remain poorly understood. Clarifying these mechanisms is crucial for a nuanced understanding and potential refinement of GC therapies in the context of cancer treatment. In HEK293T cells, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation sequencing (ChIP-seq) were used with antibodies of glucocorticoid receptor (GR) and ten-eleven translocation enzymes (TET) family proteins (TET1, TET2, TET3). Drug repositioning was performed through the Connectivity Map database, using common target genes of GR and TET2 in HEK293 and HCT116 cell lines and differentially expressed genes (DEGs) of colorectal cancer (CRC). Cell migration and invasion were tested in CRC cell lines with varying GR expression, that is, HCT116 and HT29 cell lines. Dexamethasone (Dex) treatment resulted in a significant difference in cell migration rates in two CRC cell lines with disparate GR expression levels. Co-IP and ChIP-seq analyses substantiated the interaction between GR and TET family proteins in HEK293T cells. Belinostat, the selected compound, was successfully validated for its potential to counteract the effects of GC-induced invasion in CRC cells in vitro. Transcriptomic analyses of Belinostat-treated HCT116 cells revealed down-regulation of target genes associated with cancer metastasis. This study provides valuable insights into the molecular mechanisms underlying GC-induced metastasis, introducing newly repositioned compounds that could serve as potential adjuvant therapy to GC treatment. Furthermore, it opens avenues for exploring novel drug candidates for CRC treatment.

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