miRNA‐218‐5p increases cell sensitivity by inhibiting PRKDC activity in radiation‐resistant lung carcinoma cells

Abstract

Abstract Background Non‐small cell lung carcinoma (NSCLC) is a malignancy with the highest mortality rate. Currently, surgery combined with radiotherapy is the first choice in the clinical treatment of lung carcinoma (LC); however, long‐term radiotherapy leads to radiation resistance in patients, resulting in treatment failure. Methods In this study, a new microRNA‐218‐5p (miRNA‐218‐5p) was identified, and its function in LC was investigated. Results Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) results revealed that miRNA‐218‐5p was downregulated in LC. Overexpression or inhibition of miRNA‐218‐5p in LC and targeted binding of protein kinase, DNA‐activated, catalytic polypeptide (PRKDC) to miRNA‐218‐5p were confirmed by comprehensive bioinformatic analysis. Exosomes from A549 and H1299 cells were cocultured with miRNA‐218‐5p and then cotransfected into radiation‐resistant A549R and H1299R cells; the proliferation of radiation‐resistant LC cells was found to be effectively inhibited and apoptosis was induced. Overexpression of miRNA‐218‐5p and X‐irradiation could enhance the radiosensitivity of LC cells. Exogenous miRNA‐218‐5p derived from A549 and H1299 cells could be transfected into radiation‐resistant LC cells and could inhibit PRKDC expression, thus accelerating DNA damage, apoptosis, and radiation sensitization of LC cells. Conclusions miRNA‐218‐5p could induce apoptosis and enhance the radiosensitivity of LC cells through regulatory activities, thus suggesting its application as a potential target for LC treatment.

Keywords

• exosomes
• lung carcinoma
• miRNA‐218‐5p
• PRKDC
• radiation resistance