EGFR upregulates miRNA subset to inhibit CYBRD1 and cause DDP resistance in gastric cancer

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-10-16 DOI:10.1016/j.gene.2024.149005

Xinyi Wang , Changjun Men , Shuxuan Shan , Jiayu Yang , Shuangxia Zhang , Xingming Ji , Cheng Li , Ye Wang

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引用次数: 0

Abstract

Chemoresistance is a considerable challenge for gastric cancer (GC), and the combination of cisplatin (DDP) and anti-EGFR therapy failed to show remarkable benefit. So other targets in EGFR-overexpressed and DDP-resistant GC need to be explored. Both cytological experiments and database bioinformatics analysis were applied in this study. It was confirmed that the prognosis of GC patients with EGFR oe was poor. EGFR regulated intracellular redox metabolism, enhanced GSH content and led to DDP resistance. A subset of miRNAs including miR-135b, miR-106a, miR-29a, miR-23a and miR-15a was upregulated in EGFR-overexpressed and DDP-resistant GC cells. Furthermore, EGFR inhibited CYBRD1 via enhancing the miRNA subset and scavenged the redundant ROS to cause DDP resistance. Therefore, to inhibit the miRNA subset at the same time of anti-EGFR therapy might reverse DDP resistance, serving as a potential novel drug for the future treatment of EGFR-overexpressed and DDP-resistant GC.

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表皮生长因子受体上调 miRNA 亚群抑制 CYBRD1，导致胃癌对 DDP 产生耐药性。

化疗耐药性是胃癌（GC）面临的一个巨大挑战，顺铂（DDP）和抗表皮生长因子受体（EGFR）联合疗法未能显示出显著疗效。因此，需要探索表皮生长因子受体（EGFR）过表达和DDP耐药胃癌的其他靶点。本研究应用了细胞学实验和数据库生物信息学分析。研究证实，表皮生长因子受体（EGFR）过表达的GC患者预后较差。表皮生长因子受体调控细胞内氧化还原代谢，提高了GSH含量，导致DDP耐药。包括miR-135b、miR-106a、miR-29a、miR-23a和miR-15a在内的一组miRNA在表皮生长因子受体过表达和DDP耐药的GC细胞中上调。此外，表皮生长因子受体通过增强 miRNA 子集抑制 CYBRD1，并清除多余的 ROS，从而导致 DDP 抗性。因此，在抗表皮生长因子受体（EGFR）治疗的同时抑制miRNA亚群可能会逆转DDP耐药，成为未来治疗表皮生长因子受体表达和DDP耐药GC的潜在新药。

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

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464