CircTADA2A up-regulates MAPK8 by targeting MiR-214-3p and recruiting EIF4A3 to promote the invasion and migration of non-small cell lung cancer cells

Histol Histopathol. 2023 Jul;38(7):837-848. doi: 10.14670/HH-18-529. Epub 2022 Oct 4.

Abstract

Background: Non-small cell lung cancer (NSCLC) occupies 87% of all lung cancer cases. Due to delayed diagnosis, the prognosis of NSCLC is unfavorable. To improve the survival of patients with NSCLC, more effective therapeutic targets urgently need to be identified. Recently, circular RNAs (circRNAs) have been revealed to play a crucial role in NSCLC progression.

Purpose: This research focused on the influence of circTADA2A on the malignant phenotype of NSCLC cells and its in-depth regulatory mechanisms.

Methods: RT-qPCR and western blot assays were done to examine the level of gene/protein of interest. Wound healing and transwell assays were conducted to monitor the migration and invasion of NSCLC cells. Bioinformatics tools and mechanistic assays were utilized to delve into the underlying mechanism of circTADA2A in NSCLC cells.

Results: The results demonstrated that circTADA2A presented a high expression in NSCLC. CircTADA2A knockdown was revealed to hamper migration and invasion of NSCLC cells. Mechanistically, circTADA2A elevated MAPK8 expression through sequestering miR-214-3p and recruiting EIF4A3.

Conclusion: CircTADA2A enhances MAPK8 expression by serving as a miR-214-3p sponge and EIF4A3 decoy, consequently promoting invasion and migration of NSCLC cells.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Eukaryotic Initiation Factor-4A / genetics
  • Eukaryotic Initiation Factor-4A / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • DEAD-box RNA Helicases
  • EIF4A3 protein, human
  • Eukaryotic Initiation Factor-4A
  • MicroRNAs
  • MIRN214 microRNA, human
  • TADA2A protein, human