Abstract
The oncogenic K-Ras can transform various mammalian cells and plays a critical role in development of pancreatic cancer. MicroRNAs (miRNA) have been shown to contribute to tumorigenic progression. However, the nature of miRNAs involved in K-Ras transformation remains to be investigated. Here, by using microarray we identified miR-155 as the most upregulated miRNA after both acute and prolonged activation of K-Ras in a doxycyline-inducible system. Pharmacological inhibition of MAPK and NF-κB pathway blocked the induction of miR-155 in response to K-Ras activation. Overexpression of miR-155 caused inhibition of Foxo3a, leading to decrease of major antioxidants including SOD2 and catalase, and enhanced pancreatic cell proliferation induced by ROS generation. Importantly, correlations of K-Ras, miR- 155 and Foxo3a were also validated in human pancreatic cancer tissues. Therefore, we propose that miR-155 plays an important role in oncogenic K-Ras transformation mediated by cellular redox regulation.
Original language | English (US) |
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Pages (from-to) | 21148-21158 |
Number of pages | 11 |
Journal | Oncotarget |
Volume | 6 |
Issue number | 25 |
DOIs | |
State | Published - 2015 |
Keywords
- K-Ras
- MiR-155
- Pancreatic cancer
- Reactive oxygen species
ASJC Scopus subject areas
- Oncology