LGR6 Acts as an Oncogene and Induces Proliferation and Migration of Gastric Cancer Cells

Crit Rev Eukaryot Gene Expr. 2022;32(4):11-20. doi: 10.1615/CritRevEukaryotGeneExpr.2021041271.

Abstract

Leucine rich repeat containing G protein-coupled receptor 6 (LGR6) belongs to the G protein-coupled receptor family, and it exhibits up-regulated expression in various types of human cancer. However, there are few reports of LGR6 contributing to gastric cancer (GC). Herein, we investigated the function of LGR6 and associated tumorigenic mechanisms in GC. LGR6 expression in GC was analyzed in the cancer genome atlas (TCGA) dataset and further confirmed in GC cell lines and fifteen paired tissue samples via quantitative real-time polymerase chain reaction (qRT-PCR). LGR6 expression was knocked down via small interfering RNA (siRNA), after which the impacts of silencing LGR6 on cell function were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), cell colony formation, wound-healing, and cell cycle assays. Western blot was performed to explore signaling pathways and regulatory mechanisms associated with LGR6 function. In this study, we showed that LGR6 was at higher levels in GC cell lines and gastric adenocarcinoma tissues. We found that silencing LGR6 in MKN-45 and BGC-823 cells inhibited cell proliferation and migration ability, which accompanied with an obvious regulation of MMP-9, β-catenin, CCNA2, CDK-2, and ERK1/2. In conclusion, this study demonstrated that LGR6 could act as an oncogene and may be a therapeutic target in GC.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Oncogenes
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Stomach Neoplasms* / metabolism

Substances

  • LGR6 protein, human
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled