Objective: Non-small cell lung cancer (NSCLC) occupies 85% of lung cancer. Long non-coding RNAs (LncRNAs) can regulate the radiosensitivity of cancers. This study explored the mechanism of lncRNA TRERNA1 in the radiosensitivity of NSCLC cells.
Methods: LncRNA TRERNA1 level in NSCLC cell lines was determined. NSCLC cell radiation tolerance was measured. TRERNA1 expression was silenced or overexpressed in A549/HCC827 cells with the highest/lowest radiation tolerance, respectively. The contents of γ-H2AX and SA-β-gal in NSCLC cells after radiation induction were detected. The targeted binding of TRERNA1 to miR-22-3p and miR-22-3p to SP1 were verified by dual-luciferase assay. SP1 expression were detected. Functional rescue experiments were implemented to confirm the roles of miR-22-3p and SP1 in the regulatory mechanism of TRERNA1.
Results: TRERNA1 was upregulated in NSCLC cells. TRERNA1 silencing enhanced radiosensitivity of NSCLC cells. TRERNA1 silencing elevated the contents of γ-H2AX and SA-β-gal in A549 cells after radiation induction, while TRERNA1 overexpression showed an opposite trend in HCC827 cells. There were targeting relationships between TRERNA1 and miR-22-3p, and miR-22-3p and SP1. miR-22-3p repression or SP1 overexpression abolished the effects of TRERNA1 silencing.
Conclusion: TRERNA1 silencing enhanced radiosensitivity of NSCLC cells via the miR-22-3p/SP1 axis. This study may offer new targets for NSCLC treatment.
Keywords: DNA damage repair; SP1; ionizing radiation; lncRNA TRERNA1; miR-22-3p; non-small cell lung cancer; radiosensitivity; γ-H2AX.
© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.