Evidence map›Paper›PMID 36672191›Full record

ArticleCells2023

NEK6 Regulates Redox Balance and DNA Damage Response in DU-145 Prostate Cancer Cells.

Isadora Carolina Betim Pavan, Fernanda Luisa Basei, Matheus Brandemarte Severino, Ivan Rosa E Silva, Luidy Kazuo Issayama, Mariana Camargo Silva Mancini, Mariana Marcela Góis, Luiz Guilherme Salvino da Silva, Rosangela Maria Neves Bezerra, Fernando Moreira Simabuco and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 15 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 1 institution in 1 country.

Isadora Carolina Betim PavanLaboratory of Signal Mechanisms, School of Pharmaceutical Sciences (FCF), University of Campinas (UNICAMP), Campinas 13083-871, Brazil.
Fernanda Luisa BaseiLaboratory of Signal Mechanisms, School of Pharmaceutical Sciences (FCF), University of Campinas (UNICAMP), Campinas 13083-871, Brazil.ORCID 0000-0001-6232-7170
Matheus Brandemarte SeverinoMultidisciplinary Laboratory of Food and Health, School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.ORCID 0000-0003-2124-4146
Ivan Rosa E SilvaLaboratory of Signal Mechanisms, School of Pharmaceutical Sciences (FCF), University of Campinas (UNICAMP), Campinas 13083-871, Brazil.ORCID 0000-0003-4732-1517
Luidy Kazuo IssayamaLaboratory of Signal Mechanisms, School of Pharmaceutical Sciences (FCF), University of Campinas (UNICAMP), Campinas 13083-871, Brazil.
Mariana Camargo Silva ManciniMultidisciplinary Laboratory of Food and Health, School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.
Mariana Marcela GóisMultidisciplinary Laboratory of Food and Health, School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.ORCID 0000-0002-5746-8777
Luiz Guilherme Salvino da SilvaMultidisciplinary Laboratory of Food and Health, School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.
Rosangela Maria Neves BezerraMultidisciplinary Laboratory of Food and Health, School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.
Fernando Moreira SimabucoMultidisciplinary Laboratory of Food and Health, School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, Brazil.ORCID 0000-0002-1672-9686
Jörg KobargLaboratory of Signal Mechanisms, School of Pharmaceutical Sciences (FCF), University of Campinas (UNICAMP), Campinas 13083-871, Brazil.ORCID 0000-0002-9419-0145
Universidade Estadual de Campinas (UNICAMP) · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

NEK6 is a central kinase in developing castration-resistant prostate cancer (CRPC). However, the pathways regulated by NEK6 in CRPC are still unclear. Cancer cells have high reactive oxygen species (ROS) levels and easily adapt to this circumstance and avoid cell death by increasing antioxidant defenses. We knocked out the NEK6 gene and evaluated the redox state and DNA damage response in DU-145 cells. The knockout of NEK6 decreases the clonogenic capacity, proliferation, cell viability, and mitochondrial activity. Targeting the NEK6 gene increases the level of intracellular ROS; decreases the expression of antioxidant defenses (SOD1, SOD2, and PRDX3); increases JNK phosphorylation, a stress-responsive kinase; and increases DNA damage markers (p-ATM and γH2AX). The exogenous overexpression of NEK6 also increases the expression of these same antioxidant defenses and decreases γH2AX. The depletion of NEK6 also induces cell death by apoptosis and reduces the antiapoptotic Bcl-2 protein. NEK6-lacking cells have more sensitivity to cisplatin. Additionally, NEK6 regulates the nuclear localization of NF-κB2, suggesting NEK6 may regulate NF-κB2 activity. Therefore, NEK6 alters the redox balance, regulates the expression of antioxidant proteins and DNA damage, and its absence induces the death of DU-145 cells. NEK6 inhibition may be a new strategy for CRPC therapy.

Indexed as

Prostatic Neoplasms, Castration-ResistantAntioxidantsCell Line, TumorDNA DamageHumansMaleNF-kappa B p52 SubunitNIMA-Related KinasesOxidation-ReductionReactive Oxygen SpeciesAntioxidantsNEK6 protein, humanNF-kappa B p52 SubunitNIMA-Related KinasesReactive Oxygen SpeciesapoptosisCRISPR/Cas9DDRNEK6ROS

Identifiers

PMID36672191
PMCPMC9856815
OpenAlexW4313825938

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.