Abstract
Radiotherapy resistance remains a huge hindrance in treating non-small cell lung carcinoma (NSCLC). Hyperthermia, a treatment method that raises the cell temperature to treat tumors, has been putting in clinical application combined with conventional chemotherapy and radiotherapy to enhance their effectiveness in NSCLC treatment. However, the specific mechanism of this combination therapy has not been extensively researched. In this study, we established a radiation-resistant NSCLC cell line by sequential radiation exposure. It was shown that the combination of hyperthermia and radiotherapy suppressed NSCLC xenograft tumor growth and increased radiation-induced apoptosis. Furthermore, downregulation of miR-126-5p was found in radio-resistant NSCLC cells. The results of bioinformatics analysis based on ENCORI showed that RAD50 is a direct target of miR-126-5p. Overexpressed miR-126-5p increased radiation-induced cell death by suppressing RAD50 expression. Hyperthermia treatment increases miR-126-5p and decreases RAD50, leading to more unrepaired DNA damage and greater cellular death. In conclusion, hyperthermia enhances NSCLC cells’ radio-sensitivity via miR-126-5p/RAD50 axis.
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