Oncotarget

Research Papers:

Silencing protein kinase C ζ by microRNA-25-5p activates AMPK signaling and inhibits colorectal cancer cell proliferation

Shihu Zhang, Yiyang Zhang, Qing Cheng, Zhaoqun Ma, Guanwen Gong, Zhengming Deng, Kun Xu, Gaoyuan Wang, Yousong Wei _ and Xiaoping Zou

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Oncotarget. 2017; 8:65329-65338. https://doi.org/10.18632/oncotarget.18649

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Abstract

Shihu Zhang1,*, Yiyang Zhang2,*, Qing Cheng3,*, Zhaoqun Ma1, Guanwen Gong1, Zhengming Deng1, Kun Xu1, Gaoyuan Wang1, Yousong Wei1 and Xiaoping Zou2

1Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

2Digestive Department, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, China

3Department of Gynaecology and Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China

*These authors have contributed equally to this work

Correspondence to:

Yousong Wei, email: [email protected]

Xiaoping Zou, email: [email protected]

Keywords: colorectal cancer (CRC), protein kinase C ζ (PKCζ), AMP-activated protein kinase (AMPK), microRNA-25-5p, cell proliferation

Received: March 08, 2017     Accepted: May 08, 2017     Published: June 27, 2017

ABSTRACT

Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation. Significantly, downregulation of microRNA-25-5p (miR-25-5p), a PKCζ-targeting miRNA, could be the cause of PKCζ upregulation. Exogenous expression of miR-25-5p silenced PKCζ to activate AMPK signaling, which inhibited HT-29 cell proliferation. In vivo studies showed that HT-29 xenograft growth in mice was inhibited after expressing PKCζ shRNA or miR-25-5p. Collectively, PKCζ could be a novel oncogenic protein of human CRC. PKCζ silence, by targeted-shRNA or miR-25-5p expression, activates AMPK and inhibits HT-29 cell proliferation.


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