Scholarlink

<p>Radiotherapy is a cornerstone treatment for unresectable lung cancer. However, radiation-induced bystander effects (RIBE) remain a major obstacle to its therapeutic efficacy. LINC01234, showing high expression in lung cancer RIBE, its role and mechanism remain unclear. Beas-2B cells were cultured in conditioned medium derived from A549 lung cancer cells exposed to 4.0&#xa0;Gy X-ray irradiation to establish an in vitro RIBE model. Models with LINC01234 knockdown and MECOM overexpression were constructed. Mitochondrial alterations were examined by transmission electron microscopy. The expression of ferroptosis-related and MAPK pathway–associated factors was assessed to elucidate the relationship between LINC01234 and MECOM. Co-immunoprecipitation (Co-IP) was used to investigate interactions between MECOM and JNK, p38, and Erk1/2. RIBE reduced cell viability and promoted apoptosis in bystander cells. Knockdown of LINC01234 significantly alleviated RIBE-induced injury. Mechanistically, LINC01234 silencing suppressed Fe²⁺ accumulation, ROS generation, MDA levels, GSSG, and ACSL4 expression, while enhancing GSH, GPX4, and SLC7A11 expression. In parallel, phosphorylation of JNK, p38, and Erk1/2 was inhibited. The ferroptosis inhibitor ferrostatin-1 produced effects comparable to LINC01234 knockdown. Moreover, LINC01234 silencing downregulated MECOM expression. Overexpression of MECOM reversed the protective effects of LINC01234 knockdown, whereas co-silencing LINC01234 or treatment with the MAPK pathway inhibitor osmundacetone abrogated MECOM-induced effects. Co-IP confirmed that MECOM interacts with JNK, p38, and Erk1/2. Downregulation of LINC01234 suppresses ferroptosis in RIBE cells by inhibiting MECOM-mediated phosphorylation of p38/JNK/Erk1/2, thereby mitigating radiotherapy-associated side effects.</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

Knockdown of LINC01234 suppresses radiation-induced bystander cell ferroptosis through the MECOM–MAPK signaling pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

查看全文
  • Li Wang,
  • Wanpu Wang,
  • Yuebin Shi,
  • Zhiqiang Wang,
  • Wen Deng,
  • Yang Fu,
  • Qingqing Zheng,
  • Juanjuan Zhang,
  • Xudong Feng,
  • Yong Zhang

摘要

Radiotherapy is a cornerstone treatment for unresectable lung cancer. However, radiation-induced bystander effects (RIBE) remain a major obstacle to its therapeutic efficacy. LINC01234, showing high expression in lung cancer RIBE, its role and mechanism remain unclear. Beas-2B cells were cultured in conditioned medium derived from A549 lung cancer cells exposed to 4.0 Gy X-ray irradiation to establish an in vitro RIBE model. Models with LINC01234 knockdown and MECOM overexpression were constructed. Mitochondrial alterations were examined by transmission electron microscopy. The expression of ferroptosis-related and MAPK pathway–associated factors was assessed to elucidate the relationship between LINC01234 and MECOM. Co-immunoprecipitation (Co-IP) was used to investigate interactions between MECOM and JNK, p38, and Erk1/2. RIBE reduced cell viability and promoted apoptosis in bystander cells. Knockdown of LINC01234 significantly alleviated RIBE-induced injury. Mechanistically, LINC01234 silencing suppressed Fe²⁺ accumulation, ROS generation, MDA levels, GSSG, and ACSL4 expression, while enhancing GSH, GPX4, and SLC7A11 expression. In parallel, phosphorylation of JNK, p38, and Erk1/2 was inhibited. The ferroptosis inhibitor ferrostatin-1 produced effects comparable to LINC01234 knockdown. Moreover, LINC01234 silencing downregulated MECOM expression. Overexpression of MECOM reversed the protective effects of LINC01234 knockdown, whereas co-silencing LINC01234 or treatment with the MAPK pathway inhibitor osmundacetone abrogated MECOM-induced effects. Co-IP confirmed that MECOM interacts with JNK, p38, and Erk1/2. Downregulation of LINC01234 suppresses ferroptosis in RIBE cells by inhibiting MECOM-mediated phosphorylation of p38/JNK/Erk1/2, thereby mitigating radiotherapy-associated side effects.