Oncotarget

Research Papers:

Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB

Dong Li _, Junjun Sun, Wenfang Liu, Xuan Wang, Robert Bals, Junlu Wu, Wenqiang Quan, Yiwen Yao, Yu Zhang, Hong Zhou and Kaiyin Wu

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Oncotarget. 2016; 7:66032-66050. https://doi.org/10.18632/oncotarget.11797

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Abstract

Dong Li1,*, Junjun Sun1,*, Wenfang Liu2,*, Xuan Wang3, Robert Bals4, Junlu Wu1, Wenqiang Quan1, Yiwen Yao1, Yu Zhang1, Hong Zhou1, Kaiyin Wu5

1Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China

2Department of General Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China

3Department of Pharmacy, Putuo People’s Hospital, 200060 Shanghai, China

4Department of Internal Medicine V – Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany

5Institute of Pathology, Charité Medical University, 10117 Berlin, Germany

*These authors contributed equally as first authors

Correspondence to:

Dong Li, email: 186ld@163.com

Keywords: Rig-G, lung cancer, growth inhibition, NF-κB, STAT3

Received: February 25, 2016    Accepted: August 24, 2016    Published: September 01, 2016

ABSTRACT

The expression of the retinoic acid-induced G (Rig-G) gene, an all trans retinoic acid (ATRA)-inducible gene, was observed in multiple cancer cells, including lung cancer cells. However, whether Rig-G is a tumor suppressor in lung cancer is unknown. Here, we found that ectopic expression of Rig-G can lead to a significant decrease in proliferation of lung cancer cells, resulting in an inhibition of tumor growth. Rig-G knockdown results in a modest increase in cell proliferation, as well as confers an increase in colony formation. Furthermore, transcriptome and pathway analyses of cancer cells revealed a fundamental impact of Rig-G on various growth signaling pathways, including the NF-κB pathway. Rig-G inhibits NF-κB activity by suppressing STAT3 in lung cancer cells. The downregulation of miR21 and miR181b-1 and subsequent activation of PTEN/Akt and CYLD/IκB signaling axis leading to decreased NF-κB activity required to maintain the tumor-inhibiting effect of Rig-G.. Our findings contribute to a better understanding of the antitumor effect mechanism of Rig-G, as well as offer a novel strategy for lung cancer therapy.


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