Downregulation of TRIM27 suppresses gastric cancer cell proliferation via inhibition of the Hippo-BIRC5 pathway

Pathol Res Pract. 2020 Sep;216(9):153048. doi: 10.1016/j.prp.2020.153048. Epub 2020 Jun 8.

Abstract

Although tripartite motif containing 27 (TRIM27) protein has been implicated in the progression of many cancer types, its role in gastric cancer (GC) remains poorly understood. Given that TRIM27 may be associated with the baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) gene, which is downstream of the Hippo pathway, we clarified their relationship in GC progression. In vitro cultures of 7 GC cell lines, 92 GC patient tumor samples and 46 normal clinical samples were used to examine the influence of changes in TRIM27 expression, which was assessed by quantitative PCR, immunohistochemistry, western blot analysis, and cell viability assays. We found that TRIM27 overexpression was correlated with tumor size, depth of invasion, and poor GC prognosis, while TRIM27 small interfering RNA knockdown inhibited cell proliferation and colony formation, induced apoptosis, and increased sensitivity towards 5-fluorouracil treatment in MGC-803 and HGC-27 GC cell lines. Notably, TRIM27 downregulation resulted in BIRC5 suppression via large tumor suppressor kinase 2 (LATS2) upregulation and subsequent Yes-associated protein 1 (YAP1) inhibition in MGC-803 and HGC-27 GC cell lines. In conclusion, our findings revealed the positive correlation between TRIM27 and GC progression through mediation of the Hippo-BIRC5 axis in GC.

Keywords: BIRC5; Gastric cancer; Hippo pathway; TRIM27.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survivin / metabolism*
  • Up-Regulation

Substances

  • BIRC5 protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Survivin
  • TRIM27 protein, human