Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis

Oncol Res. 2020 Feb 7;28(1):65-73. doi: 10.3727/096504019X15656904013079. Epub 2019 Sep 26.

Abstract

Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) mediate the development of esophageal squamous cell carcinoma (ESCC) via various pathophysiological pathways. This study explored the impact of the lncRNA FOXD2-AS1 on cisplatin resistance in ESCC and its possible mechanisms. Upregulation of FOXD2-AS was detected in patients with ESCC and ESCC cells that are resistant to cisplatin. In an in vitro assay, knockdown of FOXD2-AS1 noticeably inhibited cell invasion and growth, triggered cell death, and repressed the stimulation of the Akt/mTOR axis in cisplatin-resistant ESCC cells (TE-1/DDP). Conversely, the overexpression of FOXD2-AS1 remarkably increased cell invasion and growth, repressed cell death, and triggered the stimulation of the Akt/mTOR axis in TE-1/DDP cells. These findings, along with bioinformatics and validation tests, showed that FOXD2-AS1 targeted miR-195 by acting as a competing endogenous RNA. FOXD2-AS1/miR-195/Akt/mTOR axis plays a crucial role in resistance to cisplatin in ESCC cells, offering an innovative strategy to treat ESCC.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / drug therapy
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation / genetics

Substances

  • FOXD2 protein, human
  • Forkhead Transcription Factors
  • MIRN195 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA FOXD2-AS1, human
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Cisplatin