Cervical cancer is addicted to SIRT1 disarming the AIM2 antiviral defense
Abstract
Mammalian cells are equipped with antiviral innate immunity. To survive and grow, human papilloma virus (HPV)-infected cervical cancer cells must overcome this host defense system. However, the precise mechanism whereby cervical cancer cells evade the immunity is not fully understood. We noted that Sirtuin 1 (SIRT1) is overexpressed in HPV-infected cervical cancer cells and hypothesized that SIRT1 counteracts antiviral immunity. Here, we found that cervical cancer cells undergo massive death by SIRT1 knockdown, but this effect is reversed by SIRT1 restoration. SIRT1-knocked-down cells showed representative features of pyroptosis, as well as highly expressed absent in melanoma 2 (AIM2) and its downstream genes related to the inflammasome response. Mechanistically, SIRT1 repressed the NF-κB-driven transcription of the AIM2 gene by destabilizing the RELB mRNA. Interestingly, pyroptotic death signaling in SIRT1-knocked-down cells was transmitted to naïve cervical cancer cells, which was mediated by extracellular vesicles carrying AIM2 inflammasome proteins. Furthermore, the growth of cervical cancer xenografts was significantly inhibited by either SIRT1-targeting siRNAs or SIRT1-knockdown-derived extracellular vesicles. Immunohisto...Continue Reading
References
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway
Citations
The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections.
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Antivirals
Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.
Antivirals (ASM)
Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.
Addiction
This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.