LINC00163 inhibits the invasion and metastasis of gastric cancer cells as a ceRNA by sponging miR-183 to regulate the expression of AKAP12

Int J Clin Oncol. 2020 Apr;25(4):570-583. doi: 10.1007/s10147-019-01604-w. Epub 2020 Jan 1.

Abstract

Background: Gastric cancer (GC) is the most common and aggressive cancer of the digestive system and poses a serious threat to human health. Since genes do not work alone, our aim was to elucidate the potential network of mRNAs and noncoding RNAs (ncRNAs) in this study.

Methods: Transcriptome data of GC were obtained from TCGA. R and Perl were used to obtain the differentially expressed RNAs and construct a competing endogenous RNA (ceRNA) regulatory network. To investigate the biological functions of differentially expressed RNAs, loss-of-function and gain-of-function experiments were performed. Real-time PCR (RT-qPCR), western blot analysis, dual-luciferase reporter assays and fluorescence in situ hybridization were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs).

Results: Based on TCGA data and bioinformatics analysis, we identified the LINC00163/miR-183/A-Kinase Anchoring Protein 12 (AKAP12) axis. We observed that AKAP12 was weakly expressed in GC and suppressed invasion and metastasis in GC cells, which could be abolished by miR-183. In addition, LINC00163 can be used as a ceRNA to inhibit the expression of miR-183, thus enhancing the anticancer effect of AKAP12.

Conclusion: Our results demonstrated that weak LINC00163 expression in GC can sponge miR-183 to promote AKAP12. We established that the LINC00163/miR-183/AKAP12 axis plays an important role in GC invasion and metastasis and may be a potential biomarker and target for GC treatment.

Keywords: AKAP12; Gastric cancer; LINC00163; TCGA; ceRNA network; miR-183.

MeSH terms

  • A Kinase Anchor Proteins / genetics*
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • A Kinase Anchor Proteins
  • AKAP12 protein, human
  • Cell Cycle Proteins
  • MIRN183 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding