Focally amplified lncRNA on chromosome 1 regulates apoptosis of esophageal cancer cells via DRP1 and mitochondrial dynamics

IUBMB Life. 2019 Feb;71(2):254-260. doi: 10.1002/iub.1971. Epub 2018 Nov 30.

Abstract

Long noncoding RNAs (lncRNAs), a family of noncoding RNA transcripts with a length of <200 nucleotides (nts), have been associated with the pathological development of various types of carcinogenesis. Focally amplified lncRNA on chromosome 1 (FAL1) is a recently identified lncRNA. In the current study, we aimed to investigate the physiological function of FAL1 in esophageal squamous cell carcinoma (ESCC). Our findings demonstrate that FAL1 was associated with esophageal cancer cell survival by regulating mitochondrial fission. First, we found that the expression of the mitochondrial fission protein dynamin-related protein 1 (DRP1) was significantly reduced, but the expression of the mitochondrial fusion protein mitofusin 1 (Mfn1) was increased in ESCC tissues and esophageal cancer cell lines as compared with adjacent normal tissues and a normal esophagus epithelial cell line. In addition, we found that reduced expression of DRP1 in the esophageal cancer cell lines KYSE450 and EC9706 cells was associated with increased expression of FAL1. Inhibition of FAL1 promoted mitochondrial fission and mitochondrial dysfunction in KYSE450 and EC9706 cells mediated by DRP1. Silencing of DRP1 abolished FAL1-induced apoptosis through a mitochondrial-dependent pathway. Our findings suggest that FAL1/DRP1 could be a therapeutic target for the treatment of ESCC. © 2018 IUBMB Life, 71(1):254-260, 2019.

Keywords: DRP1; esophageal squamous cell carcinoma; focally amplified lncRNA on chromosome 1); long noncoding RNAs; mitochondria fission.

MeSH terms

  • Apoptosis
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Dynamins / antagonists & inhibitors
  • Dynamins / genetics*
  • Dynamins / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Dynamics / genetics*
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Mitochondrial Membrane Transport Proteins
  • Oligoribonucleotides
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • focally amplified long noncoding RNA on chromosome 1, human
  • GTP Phosphohydrolases
  • Mfn1 protein, human
  • DNM1L protein, human
  • Dynamins