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

// Dong Li 1, * , Junjun Sun 1, * , Wenfang Liu 2, * , Xuan Wang 3 , Robert Bals 4 , Junlu Wu 1 , Wenqiang Quan 1 , Yiwen Yao 1 , Yu Zhang 1 , Hong Zhou 1 , Kaiyin Wu 5 1 Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China 2 Department of General Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China 3 Department of Pharmacy, Putuo People’s Hospital, 200060 Shanghai, China 4 Department of Internal Medicine V – Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany 5 Institute of Pathology, Charite 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.