Differentially expressed long noncoding RNAs and regulatory mechanism of LINC02407 in human gastric adenocarcinoma

World J Gastroenterol. 2019 Oct 21;25(39):5973-5990. doi: 10.3748/wjg.v25.i39.5973.

Abstract

Background: Long noncoding RNAs (lncRNAs) have been identified to play important roles in the development and progression of various tumors, including gastric cancer (GC). However, the molecular role of lncRNAs in GC progression remains unclear.

Aim: To investigate the differential expression of lncRNAs in human GC and elucidate the function and regulatory mechanism of LINC02407.

Methods: The Cancer Genome Atlas database was used to investigate the involvement of lncRNAs in GC. Quantitative real-time polymerase chain reaction was used to estimate the relative expression level of LINC02407 in GC tissues and cells. Functional experiments including CCK8 assay, apoptosis assay, wound healing assay, and transwell assay were used to investigate the effect of LINC02407 on GC cells. Some microRNAs were predicted and verified via bioinformatics analysis and the luciferase reporter system. Predictive analysis and Western blot assay were used to analyze the expression of related proteins.

Results: Many differentially expressed lncRNAs were identified in GC, and some of them including LINC02407 can affect the survival. LINC02407 was upregulated in tumor tissues compared with adjacent tissues. HGC-27 cells showed the highest LINC02407 expression and HaCaT cells exhibited the lowest expression. Different experiment groups were constructed using LINC02407 overexpressing plasmids and related siRNAs. The results of functional experiments showed that LINC02407 can promote the proliferation, migration, and invasion of GC cells but inhibit apoptosis. Luciferase reporter assay showed that hsa-miR-6845-5p and hsa-miR-4455 was downstream regulated by LINC02407. Western blot analysis showed that adhesion G protein-coupled receptor D1 (ADGRD1) was regulated by the LINC02407-miR-6845-5p/miR-4455-ADGRD1 pathways.

Conclusion: LINC02407 plays a role in GC through the LINC02407-miR-6845-5p/miR-4455-ADGRD1 pathways, and thus, it may be an important oncogene and has potential value in GC diagnosis and treatment.

Keywords: Adhesion G protein-coupled receptor D1; Gastric cancer; LINC02407; Long noncoding RNAs; MicroRNA-4455; MicroRNA-6845-5p.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Apoptosis / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gastric Mucosa / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • ADGRD1 protein, human
  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptors, G-Protein-Coupled