Exosome miR-101-3p derived from bone marrow mesenchymal stem cells promotes radiotherapy sensitivity in non-small cell lung cancer by regulating DNA damage repair and autophagy levels through EZH2

Pathol Res Pract. 2024 Apr:256:155271. doi: 10.1016/j.prp.2024.155271. Epub 2024 Mar 28.

Abstract

Background and objective: The morbidity rate of non-small cell lung cancer (NSCLC) increases with age, highlighting that NSCLC is a serious threat to human health. The aim of this study was mainly to describe the role of exosomal miR-101-3p derived from bone marrow mesenchymal stem cells (BMSCs) in NSCLC.

Methods: A549 or NCI-H1703 cells (1×105/mouse) were injected into nude mice to establish an NSCLC animal model. RTqPCR, Western blotting and comet assays were used to assess the changes in gene expression, proteins and DNA damage repair.

Results: miR-101-3p and RAI2 were found to be expressed at low levels in NSCLC, while EZH2 was highly expressed. In terms of function, miR-101-3p downregulated EZH2. In addition, exosomal miR-101-3p derived from BMSCs promoted the expression of RAI2, inhibited DNA damage repair, and inhibited the activation of the PI3K/AKT/mTOR signaling pathway by inhibiting EZH2, thereby promoting autophagy and decreasing cell viability and finally enhancing the sensitivity of NSCLC to radiotherapy and inhibiting the malignant biological behavior of NSCLC.

Conclusion: Exosomal miR-101-3p derived from BMSCs can inhibit DNA damage repair, promote autophagy, enhance the radiosensitivity of NSCLC, and inhibit the progression of NSCLC by inhibiting EZH2.

Keywords: Autophagy; DNA damage repair; Exosomal miR-101–3p; Non-small cell lung cancer; Radiosensitivity.

MeSH terms

  • Animals
  • Autophagy / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Cell Proliferation
  • DNA Damage / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lung Neoplasms* / pathology
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Radiation Tolerance

Substances

  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • RAI2 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN101 microRNA, human