Silence of FAM83H-AS1 promotes chemosensitivity of gastric cancer through Wnt/β-catenin signaling pathway

Biomed Pharmacother. 2020 May:125:109961. doi: 10.1016/j.biopha.2020.109961. Epub 2020 Feb 3.

Abstract

Gastric cancer (GC) is a malignant tumor originated from the epithelium of gastric mucosa, its incidence is second only to lung cancer in China. Chemotherapy is one of the most effective methods to treat GC, but some patients are insensitive to chemotherapeutic drugs, leading to chemotherapy failure. In this study, the expression of FAM83H-AS1 was up-regulated in GC tissues and cell lines, and was related to differentiation, invasion depth and chemotherapy insensitivity of GC patients. FAM83H-AS1 was high-expressed in chemoresistant GC tissues and cell line (SGC7901/R), and silence of FAM83H-AS1 sensitized SGC7901/R cells to cisplatin (CDDP) and 5-fluorouracil (5-FU). In addition, silence of FAM83H-AS1 could inactivate Wnt/β-catenin signaling pathway in SGC7901/R cells. The activating of Wnt/β-catenin signaling pathway reversed the promoting effect of FAM83H-AS1 silence on chemotherapy sensitivity, which meant Wnt/β-catenin signaling pathway mediated the regulation of FAM83H-AS1 on chemotherapy sensitivity in SGC7901/R cells. In conclusion, FAM83H-AS1 is related with the CDDP and 5-FU insensitivity of GC patients, silence of FAM83H-AS1 promotes chemosensitivity of GC through Wnt/β-catenin signaling pathway.

Keywords: Chemosensitivity; FAM83H-AS1; Gastric cancer; Long non-coding RNA; Wnt/β-catenin signaling pathway.

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Silencing
  • Humans
  • Male
  • Proteins / genetics
  • Proteins / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / metabolism*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • FAM83H protein, human
  • Proteins
  • Wnt Proteins
  • beta Catenin
  • Cisplatin
  • Fluorouracil