Evidence map›Paper›PMID 27687727›Full record

ArticleThe Journal of biological chemistry2016

Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes.

Komal Ramani, Nirmala Mavila, Kwang Suk Ko, José M Mato, Shelly C Lu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Prohibitin 1 in liver injury and cancer.Experimental biology and medicine (Maywood, N.J.) · 2020
    Review
  10. Review
  11. Methionine adenosyltransferases in liver cancer.World journal of gastroenterology · 2019
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. The Role of Long Non-Coding RNAs in Hepatocarcinogenesis.International journal of molecular sciences · 2018
    Review
  18. Review
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

5 authors at 3 institutions in 3 countries.

Komal RamaniFrom the Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Nirmala MavilaFrom the Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Kwang Suk Kothe Department of Nutritional Science and Food Management, the College of Health Science, Ewha Womans University, Seoul 03760, Korea, and.
José M Matothe CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain.
Shelly C LuFrom the Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California 90048, shelly.lu@cshs.org.
Cedars-Sinai Medical Center · USCIC bioGUNE · ESEwha Womans University · KR

Funding

USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KAPLOWITZ, NEIL · 1995 to 2020
$21.8M
PROHIBITIN 1 IN LIVER INJURY AND CANCERR01CA172086 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LU, SHELLY CHI-LOO · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA172086NIDDK NIH HHS P30 DK048522
6 · The paper itself

Abstract

Prohibitin 1 (PHB1) is a mitochondrial chaperone that regulates cell growth. Phb1 knock-out mice exhibit liver injury and hepatocellular carcinoma (HCC). Phb1 knock-out livers show induction of tumor growth-associated genes, H19 and insulin-like growth factor 2 (Igf2). These genes are controlled by the imprinting control region (ICR) containing CCCTC-binding transcription factor (CTCF)-binding sites. Because Phb1 knock-out mice exhibited induction of H19 and Igf2, we hypothesized that PHB1-mediated regulation of the H19-Igf2 axis might control cell proliferation in normal hepatocytes. H19 and Igf2 were induced (8-20-fold) in 3-week-old Phb1 knock-out livers, in Phb1 siRNA-treated AML12 hepatocytes (2-fold), and HCC cell lines when compared with control. Phb1 knockdown lowered CTCF protein in AML12 by ∼30% when compared with control. CTCF overexpression lowered basal H19 and Igf2 expression by 30% and suppressed Phb1 knockdown-mediated induction of these genes. CTCF and PHB1 co-immunoprecipitated and co-localized on the ICR element, and Phb1 knockdown lowered CTCF ICR binding activity. The results suggest that PHB1 and CTCF cooperation may control the H19-Igf2 axis. Human HCC tissues with high levels of H19 and IGF2 exhibited a 40-50% reduction in PHB1 and CTCF expression and their ICR binding activity. Silencing Phb1 or overexpressing H19 in the mouse HCC cell line, SAMe-D, induced cell growth. Blocking H19 induction prevented Phb1 knockdown-mediated growth, whereas H19 overexpression had the reverse effect. Interestingly H19 silencing induced PHB1 expression. Taken together, our results demonstrate that the H19-Igf2 axis is negatively regulated by CTCF-PHB1 cooperation and that H19 is involved in modulating the growth-suppressive effect of PHB1 in the liver.

Indexed as

AnimalsCCCTC-Binding FactorCell Line, TumorCell ProliferationHepatocytesHumansInsulin-Like Growth Factor IILiverMiceMice, KnockoutProhibitinsRepressor ProteinsResponse ElementsRNA, Long NoncodingSignal TransductionCCCTC-Binding FactorCTCF protein, humanCtcf protein, mouseH19 long non-coding RNAIGF2 protein, humanIGF2 protein, mouseInsulin-Like Growth Factor IIPHB protein, humanProhibitinsRepressor ProteinsRNA, Long NoncodingCCCTC-binding transcription factorcell growthcell proliferationH19hepatocellular carcinomahepatocyteimprinting control regioninsulin-like growth factor 2Prohibitin 1RNA

Identifiers

PMID27687727
PMCPMC5104939
OpenAlexW2525574234

What OpenQuestion holds

Textmetadata
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.