Circ-SNAP47 (hsa_circ_0016760) and miR-625-5p are regulators of WEE1 in regulation of chemoresistance, growth and invasion of DDP-tolerant NSCLC cells via ceRNA pathway

Environ Toxicol. 2022 Feb;37(2):224-236. doi: 10.1002/tox.23391. Epub 2021 Oct 19.

Abstract

Circular RNA-synaptosome associated protein 47 (circ-SNAP47; Hsa_circ_0016760) is oncogenic in non-small-cell lung cancer (NSCLC); however, its role is undescribed in cis-diamminedichloroplatinum II (DDP) resistance. We attempted to investigate its expression, role and mechanism in DDP-tolerant NSCLC. As a result, circ-SNAP47 expression was upregulated in human DDP-tolerant NSCLC tissues and cells, accompanied with WEE1 G2 checkpoint kinase (WEE1) upregulation and microRNA (miR)-625-5p downregulation. Functionally, interfering circ-SNAP47 and/or restoring miR-625-5p curbed the 50% inhibitory concentration of DDP, colony formation, cell proliferation and invasion, accompanied with apoptotic rate promotion and depressions of multidrug resistance (MDR) markers MDR1 and MRP1, anti-apoptosis protein Bcl-2, and pro-invasion protein MMP9. Notably, circ-SNAP47 interference suppressed xenograft tumor growth of DDP-tolerant NSCLC cells by elevating miR-625-5p and descending WEE1. Mechanistically, circ-SNAP47 directly targeted miR-625-5p, and miR-625-5p further targeted WEE1. Therefore, circ-SNAP47-miR-625-5p-WEE1 axis might participate in chemoresistance and progression of DDP-tolerant NSCLC.

Keywords: DDP-tolerant NSCLC; WEE1; circ-SNAP47; miR-625-5p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Cycle Proteins* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Protein-Tyrosine Kinases* / genetics
  • RNA, Circular / genetics*

Substances

  • Cell Cycle Proteins
  • MIRN625 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • Cisplatin