Evidence map›Paper›PMID 23929703›Full record

ArticleHepatology (Baltimore, Md.)2014

Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo.

Vikash Reebye, Pål Sætrom, Paul J Mintz, Kai-Wen Huang, Piotr Swiderski, Ling Peng, Cheng Liu, Xiaoxuan Liu, Steen Lindkaer-Jensen, Dimitris Zacharoulis and 13 more

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 120 citations in OpenAlex.

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  17. Aptamers: Cutting edge of cancer therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  18. RANBP2 ActivatesCancers · 2021
    Article
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4 more citing papers are in PubMed but not listed here.

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

23 authors at 11 institutions in 8 countries.

Vikash ReebyeDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
Pål Sætrom
Paul J Mintz
Kai-Wen Huang
Piotr Swiderski
Ling Peng
Cheng Liu
Xiaoxuan Liu
Steen Lindkaer-Jensen
Dimitris Zacharoulis
Nikolaos Kostomitsopoulos
Noriyuki Kasahara
Joanna P Nicholls
Long R Jiao
Madhava Pai
Duncan R Spalding
Malkhaz Mizandari
Tinatin Chikovani
Mohamed M Emara
Abdelali Haoudi
Donald A Tomalia
John J Rossi
Nagy A Habib
Imperial College London · GBCentre Interdisciplinaire de Nanoscience de Marseille · FRCity of Hope · USQatar Foundation · QABiomedical Research Foundation of the Academy of Athens · GRNational Taiwan University · TWNorwegian University of Science and Technology · NOTbilisi State Medical University · GEUniversity Hospital of Larissa · GRUniversity of California, Los Angeles · USUniversity of Pennsylvania · US

Funding

Expression of anti-HIV siRNA in Blood CellsR01HL074704 · NHLBI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI BURNETT, JOHN CORY, ROSSI, JOHN JOSEPH · 2003 to 2015
$5.0M
YEAST SYSTEM FOR DEVELOPING ANTI-HIV-1 RIBOZYMESR01AI029329 · NIAID · LOMA LINDA UNIVERSITY · PI ROSSI, JOHN JOSEPH · 1990 to 2018
$3.9M
NHLBI NIH HHS R01 HL074704NIAID NIH HHS R01 AI029329
6 · The paper itself

Abstract

unlabelledHepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (mRNA) expression liver cancer-specific microarray in C/EBPα-saRNA-transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis, and metastasis. Up-regulated genes were enriched for tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation.

conclusionA novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model.

Indexed as

Genetic TherapyAlbuminsAnimalsCarcinoma, HepatocellularCCAAT-Enhancer-Binding Protein-alphaDrug Evaluation, PreclinicalGene Expression RegulationHep G2 CellsHumansInjections, IntravenousLiverLiver CirrhosisLiver Function TestsLiver Neoplasms, ExperimentalMaleOligonucleotide Array Sequence AnalysisAlbuminsCCAAT-Enhancer-Binding Protein-alphaIL6R protein, humanMYC protein, humanProto-Oncogene Proteins c-mycReceptors, Interleukin-6RNASTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID23929703
PMCPMC4655108
OpenAlexW2168927463

What OpenQuestion holds

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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.