Loss of FBP1 promotes proliferation, migration, and invasion by regulating fatty acid metabolism in esophageal squamous cell carcinoma

Aging (Albany NY). 2020 Nov 21;13(4):4986-4998. doi: 10.18632/aging.103916. Epub 2020 Nov 21.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China. Recent studies have shown fatty acid metabolism is involved in the progression of various cancers through regulating the function of various types of cells. However, the relationship between fatty acid metabolism and tumorigenesis of ESCC remains unclear. Here, in this study, the expression of FBP1 was dramatically decreased in ESCC tissues compared with the adjacent non-ESCC tissues. The cell proliferation, migration, invasion and fatty acid metabolism were evaluated in ESCC cells using transfection of shFBP1 vectors. We found loss of FBP1 promoted ESCC cell proliferation, migration and invasion, which correlated with the activated fatty acid metabolism in vitro. Moreover, the content of phospholipids, triglycerides, neutral lipids and the protein expression levels of fatty acid metabolism related FASN, ACC1 and SREBP1C proteins were significantly increased following down-regulation of FBP1. Furthermore, FBP1 was found to be directly targeted by miR-18b-5p in ESCC cells. In addition, miR-18b-5p inhibitor treatment obviously reversed the increased fatty acid metabolism induced by loss of FBP1 in ESCC cells. These findings explored a detailed molecular mechanism of tumorigenesis and progression of ESCC and might provide a potential novel method to treat ESCC in clinic.

Keywords: ESCC; FBP1; fatty acid metabolism; miR-18b-5p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids / metabolism
  • Fructose-Bisphosphatase / genetics
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Phospholipids / metabolism
  • RNA, Small Interfering
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • MIRN18 microRNA, human
  • MicroRNAs
  • Phospholipids
  • RNA, Small Interfering
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • FBP1 protein, human
  • Fructose-Bisphosphatase
  • ACACA protein, human
  • Acetyl-CoA Carboxylase