STAT3-induced upregulation of long noncoding RNA HNF1A-AS1 promotes the progression of oral squamous cell carcinoma via activating Notch signaling pathway

Cancer Biol Ther. 2019;20(4):444-453. doi: 10.1080/15384047.2018.1529119. Epub 2018 Nov 7.

Abstract

Long non-coding RNAs (lncRNAs) are a group of biomarkers which can regulate the biological processes of various human cancers. LncRNA HNF1A-AS1 has been reported in human cancers for its oncogenic role. This study focused on the biological function and molecular mechanism of HNF1A-AS1 in oral squamous cell carcinoma (OSCC). The high expression of HNF1A-AS1 was examined in OSCC tissues and cell lines. Kaplan Meier method revealed that high expression of HNF1A-AS1 predicted poor prognosis for patients with OSCC. Results of loss-of-function assays demonstrated that silenced HNF1A-AS1 inhibited the proliferation, migration and epithelial-mesenchymal transition (EMT) of OSCC cells. Mechanically, HNF1A-AS1 was positively regulated by the transcription factor STAT3. Recently, Notch signaling pathway has been reported in human malignancies. In this study, we analyzed the correlation between HNF1A-AS1 and Notch signaling pathway. It was uncovered that the expression of Notch1 and Hes1 (the core factors of Notch signaling pathway) was negatively regulated by HNF1A-AS1 knockdown. Rescue assays further demonstrated the positive regulatory effects of HNF1A-AS1 on Notch signaling pathway in OSCC. In conclusion, upregulation of HNF1A-SA1 induced by transcription factor STAT3 promotes OSCC progression by activating Notch signaling pathway.

Keywords: HNF1A-AS1; Notch signaling pathway; OSCC; migration; proliferation.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Survival Rate
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • NOTCH1 protein, human
  • RNA, Long Noncoding
  • Receptor, Notch1
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • long non-coding RNA HNF1A-AS1, human