Evidence map›Paper›PMID 25065598›Full record

ArticleOncogene2015

Gα12 gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma.

Y M Yang, W H Lee, C G Lee, J An, E-S Kim, S H Kim, S-K Lee, C H Lee, D N Dhanasekaran, A Moon and 5 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

33 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. GRespiratory research · 2024
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  5. GαFrontiers in cell and developmental biology · 2022
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. GαExperimental & molecular medicine · 2020
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Signaling mechanisms and physiological functions of G-protein GαProtein science : a publication of the Protein Society · 2019
    Review
  17. Article
  18. Article
  19. Article
  20. 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

15 authors at 6 institutions in 2 countries.

Y M YangCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
W H LeeCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
C G LeeCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
J AnDepartment of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
E-S KimCollege of Pharmacy, Duksung Women's University, Seoul, South Korea.
S H KimCollege of Medicine, Hanyang University, Seoul, South Korea.
S-K LeeCenter for Liver Cancer, National Cancer Center, Goyang, South Korea.
C H LeeCollege of Medicine, Hanyang University, Seoul, South Korea.
D N DhanasekaranDepartment of Cell Biology, OU Cancer Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
A MoonCollege of Pharmacy, Duksung Women's University, Seoul, South Korea.
S HwangCollege of Medicine, Hanyang University, Seoul, South Korea.
S J LeeCollege of Pharmacy, Gachon University, Incheon, South Korea.
J-W ParkCenter for Liver Cancer, National Cancer Center, Goyang, South Korea.
K M KimDepartment of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
S G KimCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Hanyang University · KRNational Cancer Center · KRSeoul National University · KRAsan Medical Center · KRDuksung Women's University · KRUniversity of Oklahoma Health Sciences Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα12 gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα12 overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα12 expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα12 (Gα12QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα12 gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα12. Decreases of miR-200a/b, -192 and -215 by Gα12 caused ZEB1 induction. The ability of Gα12 to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα12QL induced ZEB1 and other epithelial-mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα12QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα12 decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα12 level, a correlation existed in the comparison of relative changes of Gα12 and ZEB1. In conclusion, Gα12 overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial-mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα12 upregulation in liver tumor progression, implicating Gα12 as an attractive therapeutic target.

Indexed as

AnimalsCarcinoma, HepatocellularChick EmbryoDisease ProgressionEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticGTP-Binding Protein alpha Subunits, G12-G13Hep G2 CellsHumansLiver NeoplasmsMiceMice, NudeMicroRNAsOncogenesTumor Cells, CulturedTumor Suppressor Protein p53GTP-Binding Protein alpha Subunits, G12-G13MicroRNAsTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID25065598
OpenAlexW1972501434

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.