Background: Circular RNAs (circRNAs) have been reported to play roles in lung cancer development. The purpose of this work was to explore the function and mechanism of circ_0043256 in lung cancer tumorigenesis.
Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used for the detection of the levels of genes and proteins. Cell growth, angiogenesis ability, migration, and invasion were analyzed by using 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, tube formation assay, transwell assay, and murine xenograft model, respectively. The target between miR-1206 and circ_0043256 or Krüppel-like factor 2 (KLF2) was verified by dual-luciferase reporter assay.
Results: Circ_0043256 was a stable circRNA, which was found to be decreased in lung cancer tissues and cells. Functionally, forced expression of circ_0043256 suppressed lung cancer cell growth, angiopoiesis, migration, and invasion. Mechanistically, circ_0043256 directly bound to miR-1206 and miR-1206 targeted KLF2, circ_0043256 could regulate KLF2 expression via absorbing miR-1206. Rescue assay showed that miR-1206 overexpression reversed the anticancer effects of circ_0043256 on lung cancer cells. Moreover, inhibition of miR-1206 could suppress the malignant phenotypes of lung cancer cells, which was attenuated by KLF2 knockdown. Pre-clinically, lentivirus-mediated circ_0043256 overexpression impeded lung cancer growth in nude mice.
Conclusion: Forced expression of circ_0043256 could impede the tumorigenesis of lung cancer via miR-1206/KLF2 axis, indicating a potential therapeutic approach for lung cancer.
Keywords: Angiogenesis; KLF2; circ_0043256; lung cancer; miR-1206.
© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.