Hsa_circ_0079530/AQP4 Axis Is Related to Non-Small Cell Lung Cancer Development and Radiosensitivity

Ann Thorac Cardiovasc Surg. 2022 Oct 20;28(5):307-319. doi: 10.5761/atcs.oa.21-00237. Epub 2022 Jul 26.

Abstract

Background: Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of hsa_circ_0079530 (circ_0079530) in NSCLC development and radiosensitivity are largely unknown.

Methods: The abundances of circ_0079530, microRNA (miR-409-3p), aquaporin 4 (AQP4), E-cadherin, intercellular adhesion molecule-1, vitronectin, proliferating cell nuclear antigen, and matrix metalloproteinase 9 were determined via quantitative reverse transcription polymerase chain reaction or western blotting. Cell proliferation, survival fraction, cycle process, migration, invasion, and in vivo growth were examined by cell counting kit-8, colony formation, flow cytometry, transwell, and xenograft analyses. The binding relationship was assessed via dual-luciferase reporter assay and RNA immunoprecipitation assay.

Results: Circ_0079530 expression was increased in NSCLC tissues and radioresistant samples. Circ_0079530 knockdown restrained cell proliferation, migration, and invasion, and facilitated radiosensitivity. Circ_0079530 silence decreased tumor growth with or without radiation treatment. Circ_0079530 was verified as a miR-409-3p sponge, and miR-409-3p downregulation mitigated the effects of circ_0079530 interference on NSCLC cell malignancy and radiosensitivity. AQP4 was directly targeted by miR-409-3p. MiR-409-3p restrained cell proliferation, migration, and invasion, and enhanced radiosensitivity by decreasing AQP4 expression. Notably, circ_0079530 silence decreased AQP4 expression by regulating miR-409-3p expression.

Conclusion: Circ_0079530 silence repressed cell proliferation, migration, and invasion, and facilitated radiosensitivity in NSCLC cells by mediating miR-409-3p/AQP4 axis.

Keywords: AQP4; circ_0079530; miR-409-3p; non-small cell lung cancer; radiosensitivity.

MeSH terms

  • Aquaporin 4* / genetics
  • Aquaporin 4* / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Circular* / genetics
  • Radiation Tolerance / genetics
  • Treatment Outcome
  • Vitronectin / genetics
  • Vitronectin / metabolism

Substances

  • Aquaporin 4
  • Cadherins
  • Intercellular Adhesion Molecule-1
  • Matrix Metalloproteinase 9
  • MicroRNAs
  • Proliferating Cell Nuclear Antigen
  • RNA, Circular
  • Vitronectin
  • AQP4 protein, human
  • MIRN409 microRNA, human