ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-11-20 DOI:10.1016/j.tranon.2024.102203

Ying Huang , Jing Jin , Ningxin Ren , Hongxia Chen , Yan Qiao , Shuangmei Zou , Xin Wang , Linlin Zheng , Ye-Xiong Li , Wen Tan , Dongxin Lin

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引用次数: 0

Abstract

The identification a signature comprising a group of genes as markers of cancer response to chemoradiotherapy would be more appropriate and effective for predicting chemoradiotherapy efficacy. This study investigated the differentially expressed genes (DEGs) related to chemoradiotherapy resistance and established a multigene expression model for predicting the sensitivity of rectal cancer to chemoradiotherapy in rectal cancer patients, elucidated the mechanism of resistance to synchronized chemoradiotherapy. The genome-wide expression profiling microarray were performed in the tissues of 81 rectal cancer patients before neoadjuvant therapy to analyze and discover DEGs related to chemoradiotherapy resistance, and the results were verified in 45 rectal cancer patients, and finally a 20-gene signature was proposed to be a predictor of chemoradiotherapy response. Molecular biology experiments revealed that zinc finger protein 37A (ZNF37A) downregulation leads to therapeutic resistance. This study identified a 20-gene signature with group of genes can help predict the response to chemoradiotherapy of rectal cancer patients. ZNF37A demonstrated a statistically significant correlation with sensitivity to chemoradiotherapy and survival in patients with LARC who underwent chemoradiotherapy. The findings revealed that ZNF37A bound to the tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) promoter region, thereby suppressing its transcriptional activity. Reduced expression of ZNF37A induces chemoradiation resistance by inhibiting apoptosis in colorectal cancer (CRC) cells. TNFRSF6B Knockdown restored the sensitivity of CRC to chemoradiotherapy. ZNF37A is an effective modulator of chemoradiotherapy response in rectal cancer. These findings elucidate the molecular mechanism underlying chemoradiotherapy resistance and provide potential applications for individualized clinical therapy.

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ZNF37A 下调会促进 TNFRSF6B 的表达，并导致直肠癌患者对同期化放疗产生耐药性。

确定由一组基因组成的特征作为癌症对化疗放疗反应的标记将更适合和有效地预测化疗放疗的疗效。该研究调查了与化放疗耐药相关的差异表达基因（DEGs），建立了预测直肠癌患者对化放疗敏感性的多基因表达模型，阐明了同步化放疗耐药的机制。在新辅助治疗前，对81例直肠癌患者的组织进行全基因组表达谱芯片分析，发现与化疗放疗耐药相关的DEGs，并在45例直肠癌患者中进行了验证，最终提出了20个基因的特征作为化疗放疗反应的预测因子。分子生物学实验显示，锌指蛋白37A（ZNF37A）下调会导致耐药性。这项研究发现，20 个基因的特征与一组基因可帮助预测直肠癌患者对化疗放疗的反应。ZNF37A与接受化疗放疗的直肠癌患者对化疗放疗的敏感性和生存期有显著的统计学相关性。研究结果显示，ZNF37A与肿瘤坏死因子受体超家族成员6B（TNFRSF6B）启动子区域结合，从而抑制了其转录活性。ZNF37A 的表达减少会抑制结直肠癌（CRC）细胞的凋亡，从而诱导化疗耐药性。TNFRSF6B 敲除可恢复 CRC 对化放疗的敏感性。ZNF37A是直肠癌化放疗反应的有效调节剂。这些发现阐明了化放疗耐药的分子机制，并为个体化临床治疗提供了潜在的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.