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.

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.

• Authors: Can Zou, Feng Rong, Yan Zeng, Jing Zeng, Rong Wei, Dong Wei
• Journal: Environmental toxicology (Environ Toxicol) Vol. 37 Issue 2 Pg. 224-236 (Feb 2022) ISSN: 1522-7278 [Electronic] United States
• PMID: 34664776 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

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

Topics

• 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)