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

Q: What problem does this study address in NSCLC treatment?

Radiotherapy effectiveness is reduced by radioresistance in NSCLC, and the molecular basis for this resistance is not well understood.

Q: How did the study identify and confirm RAD51 as a miR-320a target?

RAD51 was predicted using bioinformatic tools and then validated as a direct post-transcriptional target using dual-luciferase reporter assays.

Sep 22, 2026

Upload by Aria Callaghan

Radiotherapy remains a key treatment for non-small cell lung cancer (NSCLC) but is limited by radioresistance. This study delineates a mechanism by which miR-320a regulates RAD51 to shape radiosensitivity and ferroptosis. miR-320a levels in NSCLC tissues and cell lines were assessed using TCGA data and qRT-PCR, while RAD51 was computationally predicted and validated via dual-luciferase reporter assays. Functional experiments showed miR-320a overexpression increases radiosensitivity by suppressing proliferation, colony formation, and migration after irradiation, accompanied by enhanced lipid ROS and reduced GPX4.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Background

Radiotherapy resistance in NSCLC

Role of microRNAs and radiosensitizing candidates

Study design and methods

Expression analysis using TCGA and qRT-PCR

Target prediction and validation of RAD51

Functional assays across radiation doses

Ferroptosis evaluation via lipid ROS and GPX4

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN miR-320a enhances radiosensitivity in non-small cell lung cancer by targeting RAD51 and modulating ferroptosis via GPX4 Jinyan Lv1,2,4, Chuanhao Zhang1,2,3,4, Xinyao Ren1, Fengwei Geng1, Shaohan Li1, Zhe Wang1,2, Xiulian Quan1, Zhichao Cheng1􀀍 & Ruoyu Wang1,2􀀍 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 asa 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. Keywords NSCLC, miR-320a, RAD51, GPX4, Radioresistance Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer diagnoses, making it the most common histological type1. The lack of distinct early clinical manifestations often results in diagnoses at advanced stages2. Radiotherapy is applicable to NSCLC across all disease stages, with nearly 50% of patients receiving this modality3. However, the development of radiotherapy resistance frequently leads to disease progression or metastasis4, and the underlying mechanisms contributing to such resistance remain poorly understood. Therefore, elucidating the mechanisms of radioresistance and identifying effective therapeutic targets are of great clinical importance. MicroRNAs (miRNAs), a major class of non-coding RNAs, are critical post-transcriptional regulators involved in both physiological homeostasis and tumor initiation and progression5,6. Owing to their stability and detectability in body fluids, miRNAs have emerged as promising biomarkers for cancer prognosis and therapeutic decision-making7–9. Numerous studies have reported that miRNAs participate in key signaling pathways and 1Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, People’s Republic of China. 2The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian 116001, People’s Republic of China. 3Graduate School of Dalian Medical University, Dalian 116044, People’s Republic of China. 4

FAQs

What problem does this study address in NSCLC treatment?

Radiotherapy effectiveness is reduced by radioresistance in NSCLC, and the molecular basis for this resistance is not well understood.

How did the study identify and confirm RAD51 as a miR-320a target?

RAD51 was predicted using bioinformatic tools and then validated as a direct post-transcriptional target using dual-luciferase reporter assays.

What did miR-320a overexpression do to NSCLC cells under radiation?

miR-320a overexpression increased radiosensitivity by inhibiting post-irradiation cell proliferation, colony formation, and migration.

Sep 22, 2026

Upload by Aria Callaghan