Circular RNA ciRS-7 promotes laryngeal squamous cell carcinoma development by inducing TGM3 hypermethylation via miR-432-5p/DNMT3B axis

Pathol Res Pract. 2022 Dec:240:154193. doi: 10.1016/j.prp.2022.154193. Epub 2022 Oct 30.

Abstract

Objective: This work is to explore the mechanism by which circular RNA ciRS-7 affects laryngeal squamous cell carcinoma (LSCC).

Methods: ciRS-7 expression in LSCC tissues was detected by qRT-PCR, and the association between ciRS-7 with clinicopathological features of LSCC patients was evaluated. HN-4 and UM-SCC-10A cells were transfected or cotransfected with si-ciRS-7, miR-432-5p inhibitor, LV-DNMT3B or si-TGM3. Then, the viability and aggressive nature of the cells were tested. The binding site between ciRS-7 and miR-432-5p or between miR-432-5p and DNMT3B was predicted and the targeting relationship was identified. The specific binding between ciRS-7 and miR-432-5p was further verified by AGO2 RIP assay. HN-4 cells transfected with si-ciRS-7 was injected into nude mice to induce xenograft tumors.

Results: Higher ciRS-7 expression in LSCC tissues was closely associated with higher clinical stage, and exacerbated infiltration and lymph node metastasis in LSCC patients. Silencing ciRS-7 inhibited LSCC cell viability, epithelial-mesenchymal transition (EMT), and promoted the apoptosis. When miR-432-5p was inhibited or DNMT3B was overexpressed, the growth and EMT of LSCC cells were stimulated despite ciRS-7 silencing. Downregulation of ciRS-7 restrained the growth of xenograft tumors in vivo.

Conclusion: ciRS-7 promotes the progression of LSCC through increasing TGM3 methylation via miR-432-5p/DNMT3B axis.

Keywords: Circular RNA ciRS-7; DNMT3B; Epithelial-mesenchymal transition; Invasion; Laryngeal squamous cell carcinoma; MiR-432–5p; Proliferation; TGM3.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Methyltransferase 3B
  • Gene Expression Regulation, Neoplastic / genetics
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Laryngeal Neoplasms* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Transglutaminases / genetics
  • Transglutaminases / metabolism

Substances

  • MicroRNAs
  • MIRN432 microRNA, human
  • RNA, Circular
  • TGM3 protein, human
  • Transglutaminases