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

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.

• Authors: Dong Li, Junjun Sun, Wenfang Liu, Xuan Wang, Robert Bals, Junlu Wu, Wenqiang Quan, Yiwen Yao, Yu Zhang, Hong Zhou, Kaiyin Wu
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 40 Pg. 66032-66050 (10 04 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27602766 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• I-kappa B Proteins
• IFIT3 protein, human
• Intracellular Signaling Peptides and Proteins
• MIRN21 microRNA, human
• MIrn181 microRNA, human
• MicroRNAs
• NF-kappa B
• STAT3 Transcription Factor
• STAT3 protein, human
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• PTEN protein, human
• CYLD protein, human
• Deubiquitinating Enzyme CYLD

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Proliferation
• Deubiquitinating Enzyme CYLD (genetics, metabolism)
• Down-Regulation
• Female
• Humans
• I-kappa B Proteins (genetics, metabolism)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• NF-kappa B (genetics, metabolism)
• PTEN Phosphohydrolase (genetics, metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• STAT3 Transcription Factor (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays