Circular RNA hsa_circ_0072309 promotes tumorigenesis and invasion by regulating the miR-607/FTO axis in non-small cell lung carcinoma

Aging (Albany NY). 2021 Apr 20;13(8):11629-11645. doi: 10.18632/aging.202856. Epub 2021 Apr 20.

Abstract

Emerging evidence has demonstrated that circular RNAs (circRNAs) are abnormally expressed in non-small cell lung carcinoma (NSCLC). However, the contributions of circRNAs to the tumorigenesis of lung adenocarcinoma (LUAD), one of the subtypes of NSCLC, remain unclear. Based on a microarray assay, we found that hsa_circ_0072309 was significantly upregulated in NSCLC compared with matched normal samples. Moreover, functional experiments demonstrated that hsa_circ_0072309 promotes the proliferation, migration, and invasion of NSCLC cells. In vitro precipitation of circRNAs, luciferase reporter assays, and biotin-coupled microRNA capture assays were carried out to investigate the mechanisms by which hsa_circ_0072309 regulates NSCLC. Through the above work, we found that hsa_circ_0072309 interacted with miR-607 via its miRNA response element to upregulate the expression of FTO, an m6A demethylase and downstream target of miR-607, thus promoting tumorigenesis of NSCLC. In total, our findings indicated the oncogenic role of hsa_circ_0072309 in NSCLC and provide a potential target for treatment.

Keywords: FTO; NSCLC; hsa_circ_0072309; miR-607; sponge effect.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Animals
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • MIRN607 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human