Scholarlink

<p>Actin gamma 1 (ACTG1) encodes the cytoskeletal protein γ-actin and is overexpressed in various cancers. Cisplatin-based chemotherapy is the standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, most patients eventually develop cisplatin resistance. The association between ACTG1 and cisplatin resistance remains unclear. In this study, we found that high expression of ACTG1 was associated with poor prognosis in NSCLC. Knockdown of ACTG1 promoted mitochondrial fragmentation via interaction with the fusion protein MFN2 and induced ferroptosis. Mechanistically, ACTG1 knockdown disrupted mitochondrial dynamics, elevated mitochondrial ROS, reduced glutathione (GSH) levels, and enhanced lipid peroxidation. This cascade significantly inhibited the growth of cisplatin-resistant NSCLC cells and sensitized them to cisplatin. Furthermore, the ferroptosis inducer RSL3 synergized with cisplatin to enhance ferroptosis and mitochondrial fragmentation, effectively sensitizing ACTG1-overexpressing cells both in vitro and in xenograft models. Our findings establish ACTG1 as a critical mediator of cisplatin resistance in NSCLC through regulation of mitochondrial integrity and ferroptosis. Targeting the ACTG1-MFN2 axis combined with ferroptosis induction represents a promising therapeutic strategy to overcome cisplatin resistance.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

ACTG1 mediates cisplatin resistance in NSCLC through induction of mitochondrial fragmentation

  • 期刊论文

  • 发表日期：

    2025年11月21日

查看全文
  • Minghua Xie,
  • Zhiming Yang,
  • Jingyue Zhou,
  • Xiaobo Chen,
  • Lisha Pu,
  • Guosheng Xiong,
  • Manjun Chen,
  • Hongwei Zhang,
  • Yunping Zhao,
  • Yanlong Yang

摘要

Actin gamma 1 (ACTG1) encodes the cytoskeletal protein γ-actin and is overexpressed in various cancers. Cisplatin-based chemotherapy is the standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, most patients eventually develop cisplatin resistance. The association between ACTG1 and cisplatin resistance remains unclear. In this study, we found that high expression of ACTG1 was associated with poor prognosis in NSCLC. Knockdown of ACTG1 promoted mitochondrial fragmentation via interaction with the fusion protein MFN2 and induced ferroptosis. Mechanistically, ACTG1 knockdown disrupted mitochondrial dynamics, elevated mitochondrial ROS, reduced glutathione (GSH) levels, and enhanced lipid peroxidation. This cascade significantly inhibited the growth of cisplatin-resistant NSCLC cells and sensitized them to cisplatin. Furthermore, the ferroptosis inducer RSL3 synergized with cisplatin to enhance ferroptosis and mitochondrial fragmentation, effectively sensitizing ACTG1-overexpressing cells both in vitro and in xenograft models. Our findings establish ACTG1 as a critical mediator of cisplatin resistance in NSCLC through regulation of mitochondrial integrity and ferroptosis. Targeting the ACTG1-MFN2 axis combined with ferroptosis induction represents a promising therapeutic strategy to overcome cisplatin resistance.