Evidence map›Paper›PMID 29632619›Full record

ArticleClinical epigenetics2018

KAT3B-p300 and H3AcK18/H3AcK14 levels are prognostic markers for kidney ccRCC tumor aggressiveness and target of KAT inhibitor CPTH2.

Elisa Cocco, Manuela Leo, Claudia Canzonetta, Serena Di Vito, Antonello Mai, Dante Rotili, Arianna Di Napoli, Andrea Vecchione, Cosimo De Nunzio, Patrizia Filetici and 1 more

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

Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

11 citing papers in PubMed, 25 citations in OpenAlex.

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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

11 authors at 5 institutions in 1 country.

Elisa Cocco1Surgical Pathology Units, Department of Clinical and Molecular Medicine, Ospedale Sant'Andrea, La Sapienza University, Rome, Italy.
Manuela Leo2Department of Biology and Biotechnology "C. Darwin", La Sapienza University of Rome, Rome, Italy.
Claudia Canzonetta3Department of Immunology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Serena Di Vito4Institute of Molecular Biology and Pathology-CNR, La Sapienza University of Rome, P.le, A. Moro 5, Rome, Italy.
Antonello Mai5Department of Drug Chemistry and Technology, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, La Sapienza University, P.le Aldo Moro, 5, 00185 Rome, Italy.
Dante Rotili5Department of Drug Chemistry and Technology, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, La Sapienza University, P.le Aldo Moro, 5, 00185 Rome, Italy.
Arianna Di Napoli1Surgical Pathology Units, Department of Clinical and Molecular Medicine, Ospedale Sant'Andrea, La Sapienza University, Rome, Italy.
Andrea Vecchione1Surgical Pathology Units, Department of Clinical and Molecular Medicine, Ospedale Sant'Andrea, La Sapienza University, Rome, Italy.
Cosimo De Nunzio6Urology Unit, Department of Clinical and Molecular Medicine, Ospedale Sant'Andrea, La Sapienza University, Rome, Italy.
Patrizia Filetici4Institute of Molecular Biology and Pathology-CNR, La Sapienza University of Rome, P.le, A. Moro 5, Rome, Italy.ORCID 0000-0001-9459-7490
Antonella Stoppacciaro1Surgical Pathology Units, Department of Clinical and Molecular Medicine, Ospedale Sant'Andrea, La Sapienza University, Rome, Italy.
Azienda Ospedaliera Sant'Andrea · ITInstitute of Molecular Biology and Pathology · ITIstituto Pasteur · ITBambino Gesù Children's Hospital · ITSapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Kidney cancer and clear cell renal carcinoma (ccRCC) are the 16th most common cause of death worldwide. ccRCC is often metastasized at diagnosis, and surgery remains the main treatment; therefore, early diagnosis and new therapeutic strategies are highly desirable. KAT inhibitor CPTH2 lowers histone H3 acetylation and induces apoptosis in colon cancer and cultured cerebellar granule neurons. In this study, we have evaluated the effects of CPTH2 on ccRCC 786-O cell line and analyzed drug targets expressed in ccRCC tumor tissues at different grade. Results: CPTH2 decreases cell viability, adhesion, and invasiveness in ccRCC cell line 786-O. It shows preferential inhibition for KAT3B-p300 with hypoacetilating effects on histone H3 at specific H3-K18. Immunohistochemical analysis of 70 ccRCC tumor tissues compared with peritumoral normal epithelium showed a statistical significant reduction of p300/H3AcK18 paralleled by an increase of H3AcK14 in G1 grade and an opposed trend during tumor progression to worst grades. In this study, we demonstrate that these marks are CPTH2 targets and significative prognosticators of low-grade ccRCC tumor. Conclusions: ccRCC is substantially insensitive to current therapies, and the efficacy of clinical treatment is dependent on the dissemination stage of the tumor. The present study shows that CPTH2 is able to induce apoptosis and decrease the invasiveness of a ccRCC cell line through the inhibition of KAT3B. In a tumor tissue analysis, we identified new prognosticator marks in grade G1 ccRCC tumors. Low KAT3B/H3AcK18 vs. high H3AcK14 were found in G1 while an opposed trend characterized tumor progression to worst grades. Our collected results suggest that CPTH2 reducing KAT3B and H3AcK18 can be considered a promising candidate for counteracting the progression of ccRCC tumors.

Indexed as

AdultAgedAged, 80 and overCarcinoma, Renal CellCell AdhesionCell Line, TumorCell ProliferationCell SurvivalE1A-Associated p300 ProteinFemaleGene Expression Regulation, NeoplasticHistonesHumansHydrazonesKidney NeoplasmsMalecyclopentylidene-(4-(4'-chlorophenyl)thiazol-2-yl)hydrazoneE1A-Associated p300 ProteinEP300 protein, humanHistonesHydrazonesThiazolesccRCCCPTH2H3-AcK18KAT3B-p300Tumor tissues

Identifiers

PMID29632619
PMCPMC5885315
OpenAlexW2805667598

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.