LncRNA WDFY3-AS2 suppresses proliferation and invasion in oesophageal squamous cell carcinoma by regulating miR-2355-5p/SOCS2 axis

J Cell Mol Med. 2020 Jul;24(14):8206-8220. doi: 10.1111/jcmm.15488. Epub 2020 Jun 14.

Abstract

Long non-coding RNAs (lncRNAs) widely participate in ESCC development and progression; however, the prognostic factors and therapeutic strategies implicated in ESCC development and progression remain to be under investigation. The purpose of the current study was to explore whether WDFY3-AS2 may be a potential prognostic factor and investigate its biological functions in ESCC. Here, WDFY3-AS2 was frequently down-regulated in ESCC tissues and cells, and its expression was correlated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Moreover, WDFY3-AS2 down-regulation significantly promoted cell proliferation and invasion, whereas WDFY3-AS2 up-regulation markedly suppressed cell proliferation and invasion in ESCC EC9706 and TE1 cells, coupled with EMT phenotype alterations. WDFY3-AS2 functioned as a competing endogenous RNA (ceRNA) for sponging miR-2355-5p, further resulted in the up-regulation of its target gene SOCS2, followed by suppression of JAK2/Stat5 signalling pathway, to suppress ESCC cell proliferation and invasion in EC9706 and TE1 cells. These findings suggest that WDFY3-AS2 may participate in ESCC development and progression, and may be a novel prognostic factor for ESCC patients, and thus targeting WDFY3-AS2/miR-2355-5p/SOCS2 signalling axis may be a novel therapeutic strategy for ESCC patients.

Keywords: WDFY3-AS2; ceRNA mechanism; invasion and metastasis; microRNA-2355-5p; oesophageal squamous cell carcinoma; suppressors of cytokine signalling 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Autophagy-Related Proteins / genetics*
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / pathology
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Janus Kinase 2
  • MicroRNAs / genetics*
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA Interference*
  • RNA, Long Noncoding / genetics*
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Survival Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Biomarkers, Tumor
  • MIRN2355 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SOCS2 protein, human
  • STAT5 Transcription Factor
  • Suppressor of Cytokine Signaling Proteins
  • WDFY3 protein, human
  • JAK2 protein, human
  • Janus Kinase 2