Analysis of co-expression networks for circular RNAs and mRNAs reveals that circular RNAs hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 are candidate oncogenes in gastric cancer

Cell Cycle. 2017;16(23):2301-2311. doi: 10.1080/15384101.2017.1380135. Epub 2017 Nov 9.

Abstract

Accumulating evidence has suggested that circular RNAs (circRNAs) play important roles in oncogenesis and tumor progression. However, our knowledge of circRNAs in gastric cancer (GC) remains limited. To investigate circRNAs involved in GC oncogenesis, we examined differentially-expressed circRNAs and mRNAs in GC tissues and paired noncancerous mucosa tissues using circRNA and mRNA microarrays. Next, we built gene co-expression networks according to the degree of correlation to predict the critical circRNAs in GC. Through bioinformatics analysis, we observed three newly identified circRNAs that are substantially upregulated in GC: hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15. Additionally, hsa_circ_0047905 and hsa_circ_0138960 positively correlated with their parental gene mRNA. Knockdown of hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 in GC cells, resulted in downregulation of parental gene expression. Functional assays suggested that inhibition of these three circular RNAs suppresses GC cell proliferation and invasion in vitro. Those findings suggest that hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 might act as tumor promoters in the pathogenesis of gastric cancer.

Keywords: Circular RNA; GDA; SERPINB5; gastric cancer; oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Guanine Deaminase / genetics
  • Guanine Deaminase / metabolism
  • Humans
  • RNA / antagonists & inhibitors
  • RNA / genetics
  • RNA / metabolism*
  • RNA Interference
  • RNA, Circular
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / metabolism
  • ROC Curve
  • Serpins / genetics
  • Serpins / metabolism
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • GDA protein, human
  • RNA, Circular
  • RNA, Messenger
  • RNA, Small Interfering
  • SERPIN-B5
  • Serpins
  • RNA
  • Guanine Deaminase

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81372291 and 81702336) and the National High-tech R&D Program (863 Program) (2015AA020110).