CircDUSP16 promotes the tumorigenesis and invasion of gastric cancer by sponging miR-145-5p

Gastric Cancer. 2020 May;23(3):437-448. doi: 10.1007/s10120-019-01018-7. Epub 2019 Nov 27.

Abstract

Background: Circular RNAs (circRNAs) as a novel subgroup of non-coding RNAs act a critical role in the pathogenesis of gastric cancer (GC). However, the underlying mechanisms by which hsa_circ_0003855 (circDUSP16) contributes to GC are still undocumented.

Materials: The differentially expressed circRNAs were identified by GEO database. The association of circDUSP16 or miR-145-5p expression with clinicopathological features and prognosis in GC patients was analyzed by FISH and TCGA-seq data set. Loss- and gain-of-function experiments as well as a xenograft tumor model were performed to assess the role of circDUSP16 in GC cells. circDUSP16-specific binding with miR-145-5p was confirmed by bioinformatic analysis, luciferase reporter, and RNA immunoprecipitation assays.

Results: The expression levels of circDUSP16 were markedly increased in GC tissue samples and acted as an independent prognostic factor of poor survival in patients with GC. Knockdown of circDUSP16 repressed the cell viability, colony formation, and invasive potential in vitro and in vivo, but ectopic expression of circDUSP16 reversed these effects. Moreover, circDUSP16 possessed a co-localization with miR-145-5p in the cytoplasm, and acted as a sponge of miR-145-5p, which attenuated circDUSP16-induced tumor-promoting effects and IVNS1ABP expression in GC cells. MiR-145-5p had a negative correlation with circDUSP16 expression and its low expression was associated with poor survival in GC patients.

Conclusions: CircDUSP16 facilitates the tumorigenesis and invasion of GC cells by sponging miR-145-5p, and may provide a novel therapeutic target for GC.

Keywords: Gastric cancer; Growth; Invasion; circDUSP16; miR-145-5p.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Dual-Specificity Phosphatases / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase Phosphatases / genetics*
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Circular / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • IVNS1ABP protein, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins
  • Transcription Factors
  • Mitogen-Activated Protein Kinase Phosphatases
  • DUSP16 protein, human
  • Dual-Specificity Phosphatases