Hsa_circ_0081534 facilitates malignant phenotypes by sequestering miR-874-3p and upregulating FMNL3 in nasopharyngeal carcinoma

Auris Nasus Larynx. 2022 Oct;49(5):822-833. doi: 10.1016/j.anl.2022.02.004. Epub 2022 Apr 12.

Abstract

Objective: Circular RNAs (circRNAs) are connected to nasopharyngeal carcinoma (NPC) development and progression. CircRNA hsa_circ_0081534 (circ_0081534) has been reported to be associated with NPC progression, but its underlying regulatory mechanisms are largely unknown. Thus, the study aims to investigate the mechanism by which circ_0081534 regulates NPC progression.

Methods: Quantitative reverse transcription polymerase chain reaction was conducted to detect circ_0081534 expression. Loss-of-function assays were conducted to evaluate the role of circ_0081534, including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation, flow cytometry, transwell, western blotting, and xenograft assays. Targeting relationship was identified through dual-luciferase reporter assay and RNA immunoprecipitation.

Results: Our data exhibited that circ_0081534 was upregulated in NPC samples and cells. Knockdown of circ_0081534 repressed NPC cell proliferation, migration, invasion, EMT, and triggered NPC cell apoptosis. Also, circ_0081534 silencing decreased NPC cell growth in xenograft models. Circ_0081534 functioned as a miR-874-3p sponge, and downregulation of miR-874-3p alleviated the suppressive effects of circ_0081534 silencing on NPC cell malignant phenotypes. MiR-874-3p targeted FMNL3, and circ_0081534 regulated FMNL3 expression through serving as a miR-874-3p sponge. Upregulation of FMNL3 relieved the inhibitory effects of circ_0081534 downregulation on NPC cell malignant phenotypes.

Conclusion: circ_0081534 interference repressed NPC progression partly by modulating the miR-874-3p/FMNL3 axis.

Keywords: FMNL3; Nasopharyngeal carcinoma; circ_0081534; miR-874-3p.

MeSH terms

  • Formins
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma* / genetics
  • Nasopharyngeal Carcinoma* / metabolism
  • Nasopharyngeal Carcinoma* / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / pathology
  • Phenotype
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism

Substances

  • FMNL3 protein, human
  • Formins
  • MIRN874 microRNA, human
  • MicroRNAs
  • RNA, Circular