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<p>Radiotherapy is an essential treatment for non-small cell lung cancer (NSCLC), but its effectiveness is often reduced by radioresistance. miR-320a has been shown to improve radiosensitivity in NSCLC, but the molecular mechanisms are not well understood. This study investigates how <i>miR-320a</i> regulates <i>RAD51</i> to affect the radiosensitivity of NSCLC. <i>miR-320a</i> expression in NSCLC tissues and cell lines was evaluated using The Cancer Genome Atlas (TCGA) data and qRT-PCR. <i>RAD51</i> was predicted as a <i>miR-320a</i> target using bioinformatic tools (TargetScan, miRDB, miRTarBase) and validated by dual-luciferase reporter assays. Functional experiments were conducted to examine the effects of <i>miR-320a</i> and <i>RAD51</i> manipulation on NSCLC cell responses to varying radiation doses. Ferroptosis was examined by measuring lipid reactive oxygen species (ROS) and <i>GPX4</i> expression levels. <i>miR-320a</i> expression was markedly reduced in NSCLC tissues and cell lines relative to normal controls and showed a positive association with clinical radiosensitivity. Functional experiments demonstrated that <i>miR-320a</i> overexpression increased radiosensitivity by inhibiting post-irradiation cell proliferation, colony formation, and migration. <i>RAD51</i> was validated as a direct post-transcriptional target of <i>miR-320a</i>. Mechanistically, <i>RAD51</i> expression inversely correlated with <i>miR-320a</i> (R = −0.16, <i>P</i> &lt; 0.001) and was associated with reduced radiosensitivity both in vitro and in patient samples. Importantly, <i>RAD51</i> knockdown reversed the radioresistance induced by <i>miR-320a</i> inhibition. Further analyses revealed that <i>RAD51</i> positively regulated <i>GPX4</i> expression, thereby suppressing ferroptosis. Inhibition of <i>RAD51</i> or restoration of <i>miR-320a</i> led to enhanced lipid peroxidation, as evidenced by increased lipid ROS accumulation and reduced <i>GPX4</i> expression, ultimately sensitizing NSCLC cells to radiotherapy. Our results indicate that <i>miR-320a</i> promotes NSCLC radiosensitivity through a negative regulation of <i>RAD51</i>. The <i>miR-320a</i>/<i>RAD51</i>/<i>GPX4</i> axis may be used as a key pathway in regulating NSCLC radiosensitivity.</p>

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miR-320a enhances radiosensitivity in non-small cell lung cancer by targeting RAD51 and modulating ferroptosis via GPX4

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月28日

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  • Jinyan Lv,
  • Chuanhao Zhang,
  • Xinyao Ren,
  • Fengwei Geng,
  • Shaohan Li,
  • Zhe Wang,
  • Xiulian Quan,
  • Zhichao Cheng,
  • Ruoyu Wang

摘要

Radiotherapy is an essential treatment for non-small cell lung cancer (NSCLC), but its effectiveness is often reduced by radioresistance. miR-320a has been shown to improve radiosensitivity in NSCLC, but the molecular mechanisms are not well understood. This study investigates how miR-320a regulates RAD51 to affect the radiosensitivity of NSCLC. miR-320a expression in NSCLC tissues and cell lines was evaluated using The Cancer Genome Atlas (TCGA) data and qRT-PCR. RAD51 was predicted as a miR-320a target using bioinformatic tools (TargetScan, miRDB, miRTarBase) and validated by dual-luciferase reporter assays. Functional experiments were conducted to examine the effects of miR-320a and RAD51 manipulation on NSCLC cell responses to varying radiation doses. Ferroptosis was examined by measuring lipid reactive oxygen species (ROS) and GPX4 expression levels. miR-320a expression was markedly reduced in NSCLC tissues and cell lines relative to normal controls and showed a positive association with clinical radiosensitivity. Functional experiments demonstrated that miR-320a overexpression increased radiosensitivity by inhibiting post-irradiation cell proliferation, colony formation, and migration. RAD51 was validated as a direct post-transcriptional target of miR-320a. Mechanistically, RAD51 expression inversely correlated with miR-320a (R = −0.16, P < 0.001) and was associated with reduced radiosensitivity both in vitro and in patient samples. Importantly, RAD51 knockdown reversed the radioresistance induced by miR-320a inhibition. Further analyses revealed that RAD51 positively regulated GPX4 expression, thereby suppressing ferroptosis. Inhibition of RAD51 or restoration of miR-320a led to enhanced lipid peroxidation, as evidenced by increased lipid ROS accumulation and reduced GPX4 expression, ultimately sensitizing NSCLC cells to radiotherapy. Our results indicate that miR-320a promotes NSCLC radiosensitivity through a negative regulation of RAD51. The miR-320a/RAD51/GPX4 axis may be used as a key pathway in regulating NSCLC radiosensitivity.