IRF8 induces senescence of lung cancer cells to exert its tumor suppressive function.

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. However, tumor suppressor genes remain to be systemically determined for lung cancer. Here we report interferon regulatory factor 8 (IRF8), a member of the IRF family of transcription factors, as a potent lung tumor suppressor gene. Expression of IRF8 is frequently diminished in lung tumoral tissues and is associated with prognosis of non-small cell lung cancer (NSCLC) patients. Ectopic expression of IRF8 suppresses the NSCLC cells proliferation in vitro and tumorigenic potential in vivo. More importantly, forced expression of IRF8 through infection of recombinant virus inhibits lung tumorigenesis in genetically engineered mouse model (GEMM). Mechanistically, IRF8 inhibits AKT signaling and promotes accumulation of P27 protein, which results in senescence of lung cancer cells. Ectopic expression of IRF8 in tumor cells leads to regression of lung cancer tumor nodules in a xenograft tumor model. Our data, therefore, solidly shows IRF8 to be a lung cancer suppressor gene and may denote an opportunity for therapeutic intervention of NSCLC.

• Authors: Jinxia Liang, Feng Lu, Bo Li, Lu Liu, Guandi Zeng, Qian Zhou, Liang Chen
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 18 Issue 23 Pg. 3300-3312 (Dec 2019) ISSN: 1551-4005 [Electronic] United States
• PMID: 31594449 (Publication Type: Journal Article)

Chemical References

• Interferon Regulatory Factors
• Tumor Suppressor Proteins
• interferon regulatory factor-8

Topics

• A549 Cells
• Animals
• Carcinogenesis (genetics)
• Carcinoma, Non-Small-Cell Lung (genetics, pathology)
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cellular Senescence (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Heterografts
• Humans
• Interferon Regulatory Factors (genetics)
• Mice
• Prognosis
• Signal Transduction (genetics)
• Tumor Suppressor Proteins (genetics)