Evidence map›Paper›PMID 30643190›Full record

ArticleOncogene2019

Mechanisms involved in the activation of C/EBPα by small activating RNA in hepatocellular carcinoma.

Xiaoyang Zhao, Vikash Reebye, Paul Hitchen, Jia Fan, Hongchi Jiang, Pål Sætrom, John Rossi, Nagy A Habib, Kai-Wen Huang

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
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  6. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Review
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  13. Article
  14. RNA splicing: a dual-edged sword for hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2022
    Review
  15. Article
  16. Review
  17. Article
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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

9 authors at 7 institutions in 5 countries.

Xiaoyang ZhaoHPB Surgery Unit, Hammersmith Hospital, Department of Surgery and Cancer, Imperial College London, London, W12 0HS, UK.ORCID http://orcid.org/0000-0002-1479-6201
Vikash ReebyeHPB Surgery Unit, Hammersmith Hospital, Department of Surgery and Cancer, Imperial College London, London, W12 0HS, UK.
Paul HitchenDepartment of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Jia FanDepartment of Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Hongchi JiangDepartment of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Pål SætromDepartment of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489, Trondheim, Norway.
John RossiDivision of Molecular Biology, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
Nagy A HabibHPB Surgery Unit, Hammersmith Hospital, Department of Surgery and Cancer, Imperial College London, London, W12 0HS, UK.
Kai-Wen HuangDepartment of Surgery and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. skywing@ntuh.gov.tw.ORCID http://orcid.org/0000-0001-6375-8714
Hammersmith Hospital · GBHarbin Medical University · CNCity of Hope · USImperial College London · GBNational Taiwan University · TWNorwegian University of Science and Technology · NOSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is generally accompanied by high mortality and low cure rate. CCAAT enhancer-binding proteins (CEBPs) are transcriptional regulators that play a key role in maintaining liver function. Altered expression of C/EBPα and C/EBPβ occurs in many tumours including HCC. saRNAs are small double-stranded RNAs that enhance target gene expression at the transcriptional level. In this report, we activate CEPBA with saRNAs and suppress CEBPB with siRNAs in cells that represent three different degrees of HCC. We performed functional assays to investigate the effects of enhancing C/EBPα and its downstream targets, p21 and albumin across these lines. We also used Mass-spectrometry (MS) subsequent to a ChIP pull-down assay to characterise the components of the protein complex involved in regulating saRNA function. Putative saRNA interacting protein candidates that were identified by MS were knocked-down with siRNAs to investigate its impact on saRNA activity. We confirmed CEBPA-saRNA decreased proliferation and migration in the differentiated lines (HepG3/Hep3B). The undifferentiated line (PLCPRF5) showed saRNA-induced increase in CEBPA but with no loss in proliferation. This effect was reversed when CEBPB was suppressed with CEBPB-siRNA. When interrogating saRNA mode of action; three saRNA interacting proteins, CTR9, HnRNPA2/B1 and DDX5 were identified by MS. Targeted knock-down of these two proteins (by siRNA) abrogated saRNA activity. This study provides insight into how different HCC lines are affected by CEBPA-saRNAs and that endogenous abundance of CEBPB and saRNA accessory proteins may dictate efficacy of CEBPA-saRNA when used in a therapeutic context.

Indexed as

Carcinoma, HepatocellularCCAAT-Enhancer-Binding ProteinsCell DifferentiationCell Line, TumorDEAD-box RNA HelicasesGene Expression RegulationHep G2 CellsHeterogeneous-Nuclear Ribonucleoprotein Group A-BHumansLiver NeoplasmsNuclear ProteinsRNA, Small InterferingCCAAT-Enhancer-Binding ProteinsCEBPA protein, humanDEAD-box RNA HelicasesHeterogeneous-Nuclear Ribonucleoprotein Group A-BNuclear ProteinsRNA, Small Interfering

Identifiers

PMID30643190
OpenAlexW2910620025

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.