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The relationship between poor prognosis in pancreatic cancer with miR-296-5p/BOK signaling axis according to a genome-wide microRNA array analysis using micro-tissues by EUS-FNA
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Hiroshi Miyamoto1,
Jun Okazaki1,
Tetsuji Takayama1 |
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1Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School |
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| Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, resistance to chemotherapy, and a poor prognosis. To clarify the molecular mechanism of them, a genome-wide microRNA (miRNA) array analysis using micro-tissues by EUS-FNA was performed. Expression of 2042 miRNAs was comprehensively profiled in 13 micro-tissues from patients with unresectable metastatic PDAC and compared with the survival periods of patients with chemotherapy. Among the miRNAs correlated with survival time in these patients, expression of miR-296-5p was predictive of shorter survival (p<0.0005). A bioinformatic analysis revealed Bcl2-related ovarian killer (BOK) as a target of miR-296-5p. Transfection of miR-296-5p mimic into pancreatic cancer cell lines, resulted in significant suppression of BOK mRNA and protein expression by qPCR and Western blotting. The transfectants showed enhanced cell invasion capability compared with control. Similarly, knock down of BOK in pancreatic cancer cells enhanced invasion capability. The transfectants of miR-296-5p mimic also showed aberrant expression of epithelial-mesenchymal transition (EMT) markers. Moreover, transfection of miR-296-5p in Panc-1 cells significantly inhibited 5-fluorouracil-induced apoptosis with a decrease of BOK expression. These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis is involved in enhanced cell invasion, drug resistance, and EMT in PDACs. |
Index Term 1: pancreatic ductal adenocarcinoma
Index Term 2: endoscopic ultrasound-fine needle aspiration
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