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MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer.
- Source :
-
Carcinogenesis [Carcinogenesis] 2017 Apr 01; Vol. 38 (4), pp. 425-431. - Publication Year :
- 2017
-
Abstract
- Pancreatic cancer is a highly aggressive malignancy, with <50% patients surviving beyond 6 months after the diagnosis, and thus, there is an urgent need to explore new diagnostic and therapeutic approaches for this disease. Therefore, we conducted microRNA (miRNA) array analysis to detect miRNA molecules potentially associated with pancreatic cancer malignancy. To assess the identified miRNAs, we performed quantitative reverse transcription-PCR on 248 pancreatic ductal adenocarcinomas (UICC stage II). We also examined miRNA expression [microRNA-21 (miR-21) and microRNA-31 (miR-31)] and epigenetic alterations, including CpG island methylator phenotype (CIMP), potentially associated with the identified miRNAs. For functional analysis, we conducted proliferation and invasion assays using a pancreatic cancer cell line. miRNA array analysis revealed that microRNA-196b (miR-196b) was the most up-regulated miRNA in pancreatic cancer tissues compared with normal pancreatic duct cells. High miR-196b expression was associated with miR-21 (P = 0.0025) and miR-31 (P = 0.0001) expression. It was also related to poor prognosis in the multivariate analysis using overall survival (hazard ratio: 1.66; 95% confidence interval: 1.09-2.54; P = 0.019). Functional analysis demonstrated that miR-196b inhibitor decreased cell proliferation and that miR-196b mimic promoted cancer cell invasion. In conclusion, a significant association of high miR-196b expression with poor prognosis was observed in pancreatic cancer. Our data also revealed that miR-196b played an oncogenic role and that the transfection of the miR-196b inhibitor had an anti-tumour effect in the pancreatic cancer cell line. These results suggest that miR-196b is a promising diagnostic biomarker and therapeutic target in pancreatic cancer.<br /> (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
Aged
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal pathology
Cell Line, Tumor
Cell Proliferation genetics
Female
Gene Expression Profiling methods
Gene Expression Regulation, Neoplastic genetics
Humans
Kaplan-Meier Estimate
Male
Neoplasm Invasiveness genetics
Prognosis
Proportional Hazards Models
Up-Regulation genetics
Biomarkers, Tumor genetics
MicroRNAs genetics
Pancreatic Neoplasms genetics
Pancreatic Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 38
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 28186267
- Full Text :
- https://doi.org/10.1093/carcin/bgx013