Evidence map›Paper›PMID 29274368›Full record

ArticleGastroenterology2018

Knockdown of Anillin Actin Binding Protein Blocks Cytokinesis in Hepatocytes and Reduces Liver Tumor Development in Mice Without Affecting Regeneration.

Shuyuan Zhang, Liem H Nguyen, Kejin Zhou, Ho-Chou Tu, Alfica Sehgal, Ibrahim Nassour, Lin Li, Purva Gopal, Joshua Goodman, Amit G Singal and 4 more

Erratum issuedAbstract read
In one paragraph

Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

71 citing papers in PubMed, 122 citations in OpenAlex.

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  14. Unveiling the cancer risk nexus of the steatotic liver.Trends in endocrinology and metabolism: TEM · 2024
    Review
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Shuyuan ZhangChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Liem H NguyenChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Kejin ZhouSimmons Comprehensive Cancer Center, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
Ho-Chou TuAlnylam Pharmaceuticals, Inc, Cambridge, Massachusetts.
Alfica SehgalAlnylam Pharmaceuticals, Inc, Cambridge, Massachusetts.
Ibrahim NassourChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Lin LiChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Purva GopalDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
Joshua GoodmanChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Amit G SingalDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Adam YoppDepartment of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
Yu ZhangChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Daniel J SiegwartSimmons Comprehensive Cancer Center, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
Hao ZhuChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Hao.Zhu@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USAlnylam Pharmaceuticals (United States) · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Reactivation of embryonic growth programs in liver cancerR01CA190525 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ZHU, HAO · 2015 to 2019
$1.8M
Enhancing mammalian liver repair and regenerationR01DK111588 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI ZHU, HAO · 2017 to 2020
$1.5M
NCI NIH HHS P30 CA142543NCI NIH HHS R01 CA190525NIDDK NIH HHS R01 DK111588
6 · The paper itself

Abstract

BACKGROUND &

aimsCytokinesis can fail during normal postnatal liver development, leading to polyploid hepatocytes. We investigated whether inhibiting cytokinesis in the liver slows tumor growth without compromising the health of normal hepatocytes. We inhibited cytokinesis in cancer cells by knocking down ANLN, a cytoskeletal scaffolding protein that regulates cytokinesis and might promote tumorigenesis, in mice with liver disease.

methodsWe analyzed clinical and gene expression data from The Cancer Genome Atlas, Oncomine, PrognoScan, and a hepatocellular carcinoma (HCC) tissue microarray. We knocked down ANLN with small interfering RNAs (siRNAs) in H2.35 liver cells and performed image analyses of cells undergoing cytokinesis. siRNAs were delivered to LAP-MYC mice, which develop hepatoblastoma, using lipid nanoparticles. H2.35 cells with knockdown of ANLN or control cells were injected into FRG mice, which develop chronic liver damage, and tumor growth was monitored. We also developed mice with inducible expression of transgenes encoding small hairpin RNAs (shRNAs) against Anln messenger RNA and studied liver tumorigenesis after administration of diethylnitrosamine and carbon tetrachloride. siRNAs against Anln messenger RNA were conjugated to N-acetylgalactosamine to reduce toxicity and increase hepatocyte tropism; their effects were studied in mouse models of liver cancer and regeneration.

resultsLevels of ANLN messenger RNA were increased in human HCC tissues compared to non-tumor liver tissues. siRNA knockdown of ANLN blocked cytokinesis in H2.35 liver cells. Administration of siRNA against ANLN increased survival times of LAP-MYC mice, compared to mice given a control siRNA. H2.35 liver cells with shRNA knockdown of ANLN formed tumors more slowly in FRG mice than control H2.35 cells. Mice with inducible expression of shRNAs against Anln mRNA developed fewer liver tumors after administration of diethylnitrosamine and carbon tetrachloride than control mice. Knockdown of ANLN did not affect liver regeneration after acute and chronic liver injuries.

conclusionsKnockdown of ANLN in liver cells blocks cytokinesis and inhibits development of liver tumors in mice. Agents that inhibit ANLN in the liver might be effective for prevention or treatment of HCC.

Indexed as

CytokinesisLiver RegenerationAnimalsCarcinoma, HepatocellularCarrier ProteinsCell LineCell Transformation, NeoplasticChemical and Drug Induced Liver InjuryGenetic Predisposition to DiseaseHepatectomyHepatocytesHumansLiver NeoplasmsMice, KnockoutMicrofilament ProteinsPhenotypeANLN protein, humanCarrier ProteinsMicrofilament ProteinsMYC protein, humanProto-Oncogene Proteins c-mycCell CycleHepatic CarcinogenesisRNA InterferenceTumorigenesis

Identifiers

PMID29274368
PMCPMC5880685
OpenAlexW2780234747

What OpenQuestion holds

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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.