MiR-7-5p functions as a tumor suppressor by targeting SOX18 in pancreatic ductal adenocarcinoma
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044 (China)
- Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People's Hospital, Beijing 100044 (China)
Highlights: • MiR-7-5p is down-regulated in pancreatic cancer tissues. • Down-regulation of miR-7-5p indicates poor prognosis for PDAC patients. • MiR-7-5p targets SOX18 to inhibit pancreatic cancer growth in vivo and vitro. • MiR-7-5p inhibits PANC-1 cell migration and invasion by targeting SOX18. • SOX18 activates JAK2/STAT3 pathway by promoting gp130 transcription. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Recently, many kinds of microRNAs (miRNAs) have been found to play a significant role in development of PDAC. However, there is no investigation about expression and function of miR-7-5p in PDAC. In this study, we found that miR-7-5p was down-regulated in PDAC tissues and its low expression level indicated a poor survival rate for PDAC patients. By bioinformatic analysis, we found that miR-7-5p targeted SOX18, and there was a negative correlation between them in PDAC tissues. Then luciferase reporter and western blot assays were used to verify the binding of miR-7-5p on SOX18 3′UTR. Cell function assays demonstrated that miR-7-5p inhibited proliferation, migration and invasion of PANC-1 cells by targeting SOX18. The nude mouse tumorigenicity assay further proved that miR-7-5p targeted SOX18 to inhibit pancreatic cancer growth in vivo. In order to further understand the mechanism, we applied a transcription factor prediction tool to explore the underlying targets that transcripted by SOX18, and the result indicated that SOX18 was a transcription factor for gp130 (a subunit of IL-6 receptor), and ChIP assays was performed to prove this prediction. Furthermore, we detected the suppression of gp130/JAK2/STAT3 signaling pathway after silencing SOX18 in PANC-1 cells, which demonstrated the transcriptional activation role of SOX18 on gp130. Thus, our present study revealed that miR-7-5p targeted SOX18 to inhibit gp130/JAK2/STAT3 signaling pathway to exert its suppressing role in PDAC.
- OSTI ID:
- 23137279
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 497, Issue 4; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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