IRF4-induced upregulation of lncRNA SOX2-OT promotes cell proliferation and metastasis in cholangiocarcinoma by regulating SOX2 and PI3K/AKT signaling

摘要

OBJECTIVE: The aim of this study was to investigate the role of lncRNA SOX2-OT in the proliferation and metastasis of cholangiocarcinoma (CCA) and its underlying mechanisms. PATIENTS AND METHODS: A total of 82 patients with CCA underwent surgery in our hospital were enrolled in this study. Five CCA cell lines (HuH-28, QBC939, HuCCT1, CCLP1, RBE) were used. The ability of proliferation and metastasis of CCA cells were detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, colony formation assay, and transwell assay, respectively. Additionally, in vivo tumor metastasis assay was done. Furthermore, the Kaplan Meier method was used to validate the prognostic importance of SOX2-OT for patients with cholangiocarcinoma. Besides, the protein and mRNA expression of CCA cells were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. RESULTS: The expression level of lncRNA SOX2-OT was significantly upregulated in cholangiocarcinoma tissues. Functional assays were further conducted to prove the oncogenic role of SOX2-OT on the proliferation and metastasis of cholangiocarcinoma cells. Furthermore, mechanism investigations manifested that transcription factor IRF4 upregulates SOX2-OT by promoting the transcriptional activity of SOX2-OT. SOX2-OT could positively regulate the nearby gene SOX2. SOX2-OT suppressed the nuclear transcription of PTEN, thereby activating PI3K/AKT signaling. CONCLUSIONS: lncRNA SOX2-OT upregulated by IRF4 promotes cell proliferation and metastasis in cholangiocarcinoma via upregulating SOX2 and activating PI3K/AKT signaling pathway.