@article{198e945d8c724b06a1596b2cb535c92c,
title = "NLRP12 suppresses hepatocellular carcinoma via downregulation of cJun N-terminal kinase activation in the hepatocyte",
abstract = "Hepatocellular carcinoma (HCC) is a deadly human cancer associated with chronic inflammation. The cytosolic pathogen sensor NLRP12 has emerged as a negative regulator of inflammation, but its role in HCC is unknown. Here we investigated the role of NLRP12 in HCC using mouse models of HCC induced by carcinogen diethylnitrosamine (DEN). Nlrp12-/- mice were highly susceptible to DEN-induced HCC with increased inflammation, hepatocyte proliferation, and tumor burden. Consistently, Nlrp12-/- tumors showed higher expression of proto-oncogenes cJun and cMyc and downregulation of tumor suppressor p21. Interestingly, antibiotics treatment dramatically diminished tumorigenesis in Nlrp12-/- mouse livers. Signaling analyses demonstrated higher JNK activation in Nlrp12-/- HCC and cultured hepatocytes during stimulation with microbial pattern molecules. JNK inhibition or NLRP12 overexpression reduced proliferative and inflammatory responses of Nlrp12-/- hepatocytes. In summary, NLRP12 negatively regulates HCC pathogenesis via downregulation of JNK-dependent inflammation and proliferation of hepatocytes.",
author = "Udden, {Sm Nashir} and Kwak, {Youn Tae} and Victoria Godfrey and Khan, {Md Abdul Wadud} and Shahanshah Khan and Nicolas Loof and Lan Peng and Hao Zhu and Hasan Zaki",
note = "Funding Information: We would like to thank the UT Southwestern Animal Resource Center (ARC) for maintenance and care of our mouse colony. We are thankful to Millennium Pharmaceuticals and Dr. Thirumala-devi Kanneganti at St. Jude Children{\textquoteright}s Research Center for sharing Nlrp12-/- mice. We also thank Dr. James S Malter at the Department of Pathology, UT Southwestern Medical Center, for critically reviewing the manuscript. This work was supported by Cancer Prevention and Research Institute of Texas (CPRIT) Individual Investigator Award (RP160169), and UT Southwestern funding given to Hasan Zaki. Hao Zhu was supported by NCI (R01CA190525) and CPRIT (RP180268) Funding Information: We would like to thank the UT Southwestern Animal Resource Center (ARC) for maintenance and care of our mouse colony. We are thankful to Millennium Pharmaceuticals and Dr. Thirumala-devi Kanneganti at St. Jude Children's Research Center for sharing Nlrp12-/- mice. We also thank Dr. James S Malter at the Department of Pathology, UT Southwestern Medical Center, for critically reviewing the manuscript. This work was supported by Cancer Prevention and Research Institute of Texas (CPRIT) Individual Investigator Award (RP160169), and UT Southwestern funding given to Hasan Zaki. Hao Zhu was supported by NCI (R01CA190525) and CPRIT (RP180268) Publisher Copyright: {\textcopyright} Udden et al.",
year = "2019",
month = apr,
doi = "10.7554/eLife.40396",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}