Oncotarget

Research Papers:

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, Zhao-lei Zeng, Wen-hua Lu, Jing Yang, Shijun Wen, Paul J. Chiao, Yumin Hu and Peng Huang _

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Oncotarget. 2015; 6:21148-21158. https://doi.org/10.18632/oncotarget.4125

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Abstract

Peng Wang1,2,*, Chao-feng Zhu1,*, Ming-zhe Ma1,*, Gang Chen3,*, Ming Song1, Zhao-lei Zeng1, Wen-hua Lu1, Jing Yang1, Shijun Wen1, Paul J. Chiao4, Yumin Hu1 and Peng Huang1,3

1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China

2 Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Guangzhou, China

3 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

4 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

* These authors contributed equally to this work

Correspondence to:

Yumin Hu, email:

Peng Huang, email:

Keywords: K-Ras, miR-155, reactive oxygen species, pancreatic cancer

Received: November 05, 2014 Accepted: May 02, 2015 Published: May 12, 2015

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.


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