Micro-RNA-155 is induced by K-Ras oncogenic signal and promotes ROS stress in pancreatic cancer

Peng Wang, Chao feng Zhu, Ming zhe Ma, Gang Chen, Ming Song, Zhaolei Zeng, Wen hua Lu, Jing Yang, Shijun Wen, Paul J. Chiao, Yumin Hu, Peng Huang

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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 languageEnglish (US)
Pages (from-to)21148-21158
Number of pages11
JournalOncotarget
Volume6
Issue number25
DOIs
StatePublished - 2015

Keywords

  • K-Ras
  • MiR-155
  • Pancreatic cancer
  • Reactive oxygen species

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Micro-RNA-155 is induced by K-Ras oncogenic signal and promotes ROS stress in pancreatic cancer'. Together they form a unique fingerprint.

Cite this