Evidence map›Paper›PMID 33413510›Full record

ArticleJournal of hematology & oncology2021

Hepatic NOD2 promotes hepatocarcinogenesis via a RIP2-mediated proinflammatory response and a novel nuclear autophagy-mediated DNA damage mechanism.

Yi Zhou, Liang Hu, Wenqing Tang, Dongping Li, Lijie Ma, Hongchun Liu, Shuncai Zhang, Xiaojie Zhang, Ling Dong, Xizhong Shen and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 95 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 1 country.

Yi ZhouDepartment of Biochemistry and Molecular Biology, NHC Key Laboratory of Glycoconjugates Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Liang HuDepartment of Cardiology, the First Affiliated Hospital of Zhengzhou University, Cardiovascular Institute of Zhengzhou University, Zhengzhou, China.
Wenqing TangDepartment of Biochemistry and Molecular Biology, NHC Key Laboratory of Glycoconjugates Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Dongping LiDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Lijie MaDepartment of General Surgery, Zhongshan Hospital (South), Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Hongchun LiuDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shuncai ZhangDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Xiaojie ZhangDepartment of Rheumatology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Ling DongDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Xizhong ShenDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
She ChenDepartment of Biochemistry and Molecular Biology, NHC Key Laboratory of Glycoconjugates Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. shechen@fudan.edu.cn.
Ruyi XueDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. xue.ruyi@zs-hospital.sh.cn.
Si ZhangDepartment of Biochemistry and Molecular Biology, NHC Key Laboratory of Glycoconjugates Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. zhangsi@fudan.edu.cn.ORCID 0000-0002-5682-4995
Fudan University · CNShanghai Medical College of Fudan University · CNFirst Affiliated Hospital of Zhengzhou University · CNQilu Hospital of Shandong University · CNShanghai Public Health Clinical Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKey hepatic molecules linking gut dysbiosis and hepatocarcinogenesis remain largely unknown. Gut-derived gut microbiota contains pathogen-associated molecular patterns (PAMPs) that may circulate into the liver and, consequently, be recognized by hepatic pattern recognition receptors (PRRs). NOD2, a general intracellular PRR, recognizes muramyl dipeptide (MDP), present in both gram (+) and gram (-) bacteria. Here, we investigated the role of NOD2 as a molecular sensor translating gut dysbiosis signaling into hepatocarcinogenesis.

methodsNOD2 expression was measured in clinical hepatocellular carcinoma (HCC) samples using qPCR (80 pairs), western blotting (30 pairs) and immunostaining (141 pairs). The role of NOD2 in hepatocarcinogenesis was examined in the hepatocyte-specific Nod2-knockout (Nod2

resultsNOD2 was upregulated and activated in HCC samples, and high NOD2 expression correlated with poor prognosis in HCC patients. Hepatic NOD2 deletion in vivo decreased DEN/CCl

conclusionsWe reveal a novel bridge, bacterial sensor NOD2, linking gut-derived microbial metabolites to hepatocarcinogenesis via induction of the inflammatory response and nuclear autophagy. Thus, we propose hepatic NOD2 as a promising therapeutic target against HCC.

Indexed as

AnimalsAutophagyCarcinogenesisCarcinoma, HepatocellularDNA DamageGene Expression Regulation, NeoplasticGene Knockout TechniquesHumansInflammationLiver NeoplasmsMiceNod2 Signaling Adaptor ProteinReceptor-Interacting Protein Serine-Threonine Kinase 2NOD2 protein, humanNod2 protein, mouseNod2 Signaling Adaptor ProteinReceptor-Interacting Protein Serine-Threonine Kinase 2RIPK2 protein, humanRipk2 protein, mouseCDNA damageHepatocellular carcinomaLamin ANOD2Nuclear autophagyRIP2

Identifiers

PMID33413510
PMCPMC7791875
OpenAlexW3118466220

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.