Translation regulatory long non-coding RNA 1 negatively regulates cell radiosensitivity via the miR-22-3p/SP1 axis in non-small cell lung cancer

Clin Respir J. 2024 Jan;18(1):e13734. doi: 10.1111/crj.13734.

Abstract

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.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / radiotherapy
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • Radiation Tolerance / genetics
  • Sp1 Transcription Factor / genetics

Substances

  • MicroRNAs
  • MIRN22 microRNA, human
  • RNA, Long Noncoding
  • tre long noncoding RNA, human
  • Sp1 Transcription Factor