Journal
TUMOR BIOLOGY
Volume 37, Issue 12, Pages 16053-16063Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-016-5445-8
Keywords
Drug resistance; 5-Fluorouracil; miR-221-3p; RB1; Pancreatic cancer
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Funding
- National Natural Science Foundation of China [31371322, 91440111, 31571523]
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Pancreatic cancer is a highly lethal disease due to its rapid dissemination and resistance to conventional chemo therapy. MicroRNAs (miRNAs) are emerging as novel regulators of chemoresistance, which modulate the expression of drug resistance-related genes. MiRNA-221 has been reported to be associated with chemoresistance in various types of cancer. But the detailed molecular mechanism about miR-221-3p regulating 5-fluorouracil (5-FU) resistance in human pancreatic cancer remains to be clarified. In this study, we investigated the association between miR-221-3p expression and 5FU sensitivity. Studies on pancreatic cancer cell lines suggested an increased 5-FU resistance with miR-221-3p overexpression. In addition, the results indicated that miR-221-3p down-regulated RB1 expression by directly binding to its 3'-UTR and therefore caused increased several aspects of pancreatic cancer pathogenesis, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Collectively, our findings revealed the important role of miR-221-3p in promoting 5-FU resistance of pancreatic cancer cells and provided a potential therapeutic target for pancreatic cancer.
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