Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB.
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.
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Dong
D
Li
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Junjun
J
Sun
Department of General Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Wenfang
W
Liu
Department of Pharmacy, Putuo People's Hospital, 200060 Shanghai, China.
Xuan
X
Wang
Department of Internal Medicine V - Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
Robert
R
Bals
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Junlu
J
Wu
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Wenqiang
W
Quan
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Yiwen
Y
Yao
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Yu
Y
Zhang
Department of Clinical Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China.
Hong
H
Zhou
Institute of Pathology, Charité Medical University, 10117 Berlin, Germany.
Kaiyin
K
Wu
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D000074749:Deubiquitinating Enzyme CYLD / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D020672:I-kappa B Proteins; C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C524940:MIRN21 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
NF-κB; Rig-G; STAT3; growth inhibition; lung cancer