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

摘要

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.