Circ_0000218 plays a carcinogenic role in laryngeal cancer through regulating microRNA-139-3p/Smad3 axis

Pathol Res Pract. 2020 Sep;216(9):153103. doi: 10.1016/j.prp.2020.153103. Epub 2020 Jul 10.

Abstract

Background: Laryngeal squamous cell carcinoma (LSCC) accounts for about 85%-90% of all cases of laryngeal cancer. So far, the role and molecular mechanism of circular RNA 0,000,218 (circ_0000218)/microRNA (miR)-139-3p in laryngeal cancer are not clear. The present study aimed to investigate the role and regulatory mechanism of circ_0000218/miR-139-3p in laryngeal cancerin vitro and in vivo.

Methods: quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0000218/miR-139-3p in LSCC cells. Dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm binding sites between miR-139-3p and smad family member 3 (Smad3), and circ_0000218 and miR-139-3p. Cell Counting Kit-8 (CCK-8) and cell apoptosis analysis were used to detect cell viability and apoptosis. Xenograft experiment was performed to show in vivo effect of circ_0000218/miR-139-3p on the growth of LSCC.

Results: Circ_0000218 was highly expressed in LSCC cells. miR-139-3p, lower expressed in LSCC cells, was negatively regulated by circ_0000218 in LSCC cells. Besides, the findings suggested that circ_0000218 silencing inhibited the LSCC cell viability and promoted apoptosis by negatively regulating miR-139-3p expression. Furthermore, the data indicated that miR-139-3p inhibited the viability of LSCC cells and promoted apoptosis, and these effects were reversed by Smad3 over-expression. In addition, the in vivo effects of circ_0000218/miR-139-3p on LSCC were consistent with the in vitro study.

Conclusions: circ_0000218 inhibition inhibited the growth of LSCC by targeting miR-139-3p/Smad3 axis. Our present study provided a new target for laryngeal cancer treatment.

Keywords: Laryngeal cancer; Smad3; circ_0000218; microRNA-139-3p.

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Carcinogenesis / genetics
  • Carcinogens / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Smad3 Protein / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Apoptosis Regulatory Proteins
  • Carcinogens
  • MIRN139 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • SMAD3 protein, human
  • Smad3 Protein