Cervical cancer is addicted to SIRT1 disarming the AIM2 antiviral defense

Oncogene
Daeho SoJong-Wan Park

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

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Citations

Mar 10, 2019·Immunology·Qiuli YangGuangwei Liu
Sep 11, 2019·Cell Death & Disease·Xiaojing XiaJianhe Hu
Aug 12, 2020·Journal of Hematology & Oncology·Rong TangSi Shi
Nov 5, 2020·Antioxidants & Redox Signaling·Congying PuMin Huang
Feb 20, 2021·Cell Death & Disease·Martina RaudenskáMichal Masařík
Mar 16, 2019·Current Opinion in Chemical Biology·Tatsiana KosciukHening Lin
Mar 16, 2021·Frontiers in Oncology·Lei WangPengfei Ge
Mar 30, 2021·Signal Transduction and Targeted Therapy·Pian YuXiang Chen
May 21, 2021·Immunity, Inflammation and Disease·Huan ZhuHaijing Wu
Oct 1, 2021·The Journal of International Medical Research·Jianxiu DuanShengdan Nie

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Methods Mentioned

BETA
flow cytometry
transfection
ChIP
transmission electron microscopy
xenograft
xenografts
protein assay
immunoprecipitation
PCR
Assay

Software Mentioned

MetaMorph
ImageJ
DAVID
LASAGNA
Multiple Experiment Viewer
- Search
histoscore
SPSS

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