Downregulation of SNHG1 suppresses cell proliferation and invasion by regulating Notch signaling pathway in esophageal squamous cell cancer

Cancer Biomark. 2017 Dec 12;21(1):89-96. doi: 10.3233/CBM-170286.

Abstract

Background: Long non-coding RNAs (lncRNAs) exert important functions involved in tumorigenesis and cancer progression including esophageal squamous cell cancer (ESCC), however, the clinical role and underlying biological function of Small Nucleolar RNA Host Gene 1 (SNHG1) in ESCC is not well known.

Methods: Quantitative Real-time polymerase chain reaction (QRT-PCR) was used to detect the SNHG1 expression levels in ESCC tissues and adjacent non-cancerous tissues. Chi-square test was used to evaluate the association between clinicopathological features and SNHG1 expression in ESCC patients, Kaplan-Meier curve and log rank test was performed to analyze the association between overall survival and SNHG1 expression. Cell proliferation and invasion was assessed by MTT assay, colony formation, and transwell cell invasion assays. Western blot were also performed to examine protein expression levels of E-cadherin, Vimentin and N-cadherin, Notch 1 and Hes-1.

Results: We demonstrated that lncRNA SNHG1 was significantly up-regulated in ESCC tissues compared with adjacent non-cancerous tissues in ESCC patients. Meanwhile, increased lncRNA SNHG1 expression levels markedly correlated with lymph node metastasis, depth of invasion, TNM stage and reduced over survival time in ESCC patients. Furthermore, MTT assay, colony formation, transwell cell invasion, qRT-PCR and Western-blot assays demonstrated that knockdown of lncRNA SNHG1 could inhibit cell proliferation and cell invasion capacity and cell Epithelial-Mesenchymal Transition (EMT) phenomenon by up-regulation E-cadherin and down-regulating Vimentin and N-cadherin in ESCC cells. Besides, we demonstrated that knockdown of SNHG1 suppressed the Notch signaling pathway by reducing the Notch1 and Hes-1 expression levels in ESCC cells.

Conclusions: These results indicated that lncRNA SNHG1 may be a potential predictor of prognosis in ESCC patients and a novel target for ESCC treatment.

Keywords: Long non-coding RNA; SNHG1; cell invasion; cell proliferation; esophageal squamous cell cancer.

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Down-Regulation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Signal Transduction / genetics

Substances

  • RNA, Long Noncoding
  • Receptor, Notch1
  • long non-coding RNA SNHG1, human