Evidence map›Paper›PMID 29290764›Full record

ArticleJournal of Cancer2018

Aminoacylase 3 Is a New Potential Marker and Therapeutic Target in Hepatocellular Carcinoma.

Kirill Tsirulnikov, Sergio Duarte, Anamika Ray, Nakul Datta, Ali Zarrinpar, Lin Hwang, Kym Faull, Alexander Pushkin, Ira Kurtz

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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 3 institutions in 1 country.

Kirill TsirulnikovDivision of Nephrology, Department of Medicine, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Sergio DuarteDumont-UCLA Transplant Center, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Anamika RayDepartment of Surgery, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Nakul DattaDepartment of Surgery, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Ali ZarrinparDepartment of Surgery, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Lin HwangPasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Kym FaullPasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Alexander PushkinDivision of Nephrology, Department of Medicine, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Ira KurtzDivision of Nephrology, Department of Medicine, D. Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
University of California, Los Angeles · USInnoSense (United States) · USUniversity of Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ras proteins (HRas, KRas and NRas) are common oncogenes that require membrane association for activation. Previous approaches to block/inhibit Ras membrane association were unsuccessful for cancer treatment in human clinical studies. In the present study we utilized a new approach to decrease Ras membrane association in hepatocellular carcinoma (HCC) cell lines via inhibition of an enzyme aminoacylase 3 (AA3; EC 3.5.1.114). AA3 expression was significantly elevated in the livers of HCC patients and HCC cell lines. Treatment of HepG2 cells with AA3 inhibitors, and HepG2 and HuH7 with AA3 siRNA significantly decreased Ras membrane association and was toxic to these HCC cell lines. AA3 inhibitors also increased the levels of N-acetylfarnesylcysteine (NAFC) and N-acetylgeranylgeranylcysteine (NAGGC) in HepG2 and Huh7 cell lines. We hypothesized that AA3 deacetylates NAFC and NAGGC, and generated farnesylcysteine (FC) and geranylgeranylcysteine (GGC) that are used in HCC cells for the regeneration of farnesylpyrophosphate and geranylgeranylpyrophosphate providing the prenyl (farnesyl or geranylgeranyl) group for Ras prenylation required for Ras membrane association. This was confirmed experimentally where purified human AA3 was capable of efficiently deacetylating NAFC and NAGGC. Our findings suggest that AA3 inhibition may be an effective approach in the therapy of HCC and that elevated AA3 expression in HCC is potentially an important diagnostic marker.

Indexed as

aminoacylase 3.hepatocellular carcinomaRas prenylation

Identifiers

PMID29290764
PMCPMC5743706
OpenAlexW2768587383

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.