circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma

Mol Carcinog. 2019 Oct;58(10):1783-1794. doi: 10.1002/mc.23065. Epub 2019 Jun 17.

Abstract

Recent findings have shown that dysregulation of circular RNAs (circRNAs) is implicated in various cancers. However, the contribution of circRNAs in oral squamous cell carcinoma (OSCC) remains largely unexplored. We screened circRNA expression profiles using a circRNA microarray in paired OSCC and normal tissues and explored the clinical significance of a downregulated circRNA, circ-PKD2. Moreover, the biological function of circ-PKD2 in OSCC was investigated both in vitro and in vivo. We found that downregulation of circ-PKD2 in OSCC correlated significantly with aggressive characteristics. Further analysis revealed that overexpression of circ-PKD2 inhibited OSCC cell proliferation, migration and invasion, induced apoptosis and cell cycle arrest, which were promoted by knockdown of circ-PKD2. In addition, circ-PKD2 was identified as a sponge for miR-204-3p and upregulated the expression of adenomatous polyposis coli 2 (APC2), which was the functional target of miR-204-3p. Moreover, circ-PKD2 attenuated the oncogenic effects of miR-204-3p-mediated APC2 on OSCC progression via multiple signaling pathways. These results demonstrate that the circ-PKD2/miR-204-3p/APC2 axis represents a novel pathway involved in the pathogenesis of OSCC and may serve as a novel therapeutic target of OSCC.

Keywords: APC2; circ-PKD2; miR-204-3p; oral squamous cell carcinoma; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytoskeletal Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Microarray Analysis
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / therapy
  • Protein Kinase D2
  • Protein Kinases / genetics*
  • Protein Kinases / therapeutic use
  • RNA, Circular / genetics
  • RNA, Circular / therapeutic use
  • Signal Transduction

Substances

  • APC2 protein, human
  • Cytoskeletal Proteins
  • MIRN204 microRNA, human
  • MicroRNAs
  • Protein Kinase D2
  • RNA, Circular
  • Protein Kinases