Evidence map›Paper›PMID 28100270›Full record

ArticleJournal of experimental & clinical cancer research : CR2017

Pro-inflammation NF-κB signaling triggers a positive feedback via enhancing cholesterol accumulation in liver cancer cells.

Mingyan He, Wenhui Zhang, Yinying Dong, Lishun Wang, Tingting Fang, Wenqing Tang, Bei Lv, Guanglang Chen, Biwei Yang, Peixin Huang and 1 more

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

Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 21% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
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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

11 authors at 3 institutions in 1 country.

Mingyan HeLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Wenhui ZhangCancer Hospital of Baotou City, Inner Monggolia, 014030, China.
Yinying DongLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Lishun WangMinhang Hospital, Fudan University, Shanghai, 201100, China.
Tingting FangLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Wenqing TangLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Bei LvLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Guanglang ChenMinhang Hospital, Fudan University, Shanghai, 201100, China.
Biwei YangLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Peixin HuangLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jinglin XiaLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. xiajinglin@fudan.edu.cn.
Fudan University · CNZhongshan Hospital · CNMinhang District Central Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) develops in a complex microenvironment characterized by chronic inflammation. In recent years, cholesterol metabolic abnormalities have been implicated the importance in cancer cell physiology. This study was designed to investigate the relationship between inflammation and cholesterol accumulation in HCC cells.

methodsHuman HCC cells HepG2 and Huh7 were cultured and stimulated with lipopolysaccharide (LPS) for 24 h. The changes of HCC cells related to cholesterol metabolism including intracellular cholesterol concentrations, cholesterol uptake, and the expression of cholesterol-related genes 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), LDL receptor (LDLR), sterol regulatory element-binding transcription factor 2 (SREBF2), and proprotein convertase subtilisin/kexin 9 (PCSK9) were comparatively analyzed. Simultaneously, the effects of nuclear factor-kappa B (NF-κB) signaling pathway on cholesterol metabolism were clarified by knocking-down of nuclear factor kappa-B kinase subunit alpha (IKKα) and TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (TAB3) via RNAi and microRNA (miR)-195. Subsequently, the roles of cholesterol accumulation in LPS induced pro-inflammatory effects were further investigated.

resultsPro-inflammatory factor LPS significantly increased intracellular cholesterol accumulation by upregulating the expression of HMGCR, LDLR, and SREBF2, while downregulating the expression of PCSK9. These effects were revealed to depend on NF-κB signaling pathway by knocking-down and overexpression of IKKα and TAB3. Additionally, miR-195, a regulator directly targeting IKKα and TAB3, blocked the effects of cholesterol accumulation, further supporting the critical role of pro-inflammation NF-κB signaling in regulating cholesterol accumulation. Intriguingly, the accumulation of cholesterol conversely exerted an augmented pro-inflammation effects by further activating NF-κB signaling pathway.

conclusionsThese results indicated that pro-inflammation effects of NF-κB signaling could be augmented by a positive feedback via enhancing the cholesterol accumulation in liver cancer cells.

Indexed as

Carcinoma, HepatocellularCell Line, TumorCholesterolFeedback, PhysiologicalGene Expression Regulation, NeoplasticHep G2 CellsHumansHydroxymethylglutaryl CoA ReductasesLipopolysaccharidesLiver NeoplasmsNF-kappa BProprotein Convertase 9Receptors, LDLSignal TransductionSterol Regulatory Element Binding Protein 2CholesterolHMGCR protein, humanHydroxymethylglutaryl CoA ReductasesLDLR protein, humanLipopolysaccharidesNF-kappa BPCSK9 protein, humanProprotein Convertase 9Receptors, LDLSREBF2 protein, humanSterol Regulatory Element Binding Protein 2Cholesterol accumulationHepatocellular carcinomaLipopolysaccharidemicroRNA-195Nuclear factor-kappa B

Identifiers

PMID28100270
PMCPMC5242086
OpenAlexW2575811573

What OpenQuestion holds

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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.