Evidence map›Paper›PMID 36212716›Full record

ArticleBioMed research international2022

KDOAM-25 Overcomes Resistance to MEK Inhibitors by Targeting KDM5B in Uveal Melanoma.

Hongjun Zhang, Xiangnan Liu, Yong'an Chen, Rui Xu, Shengli He

RetractedOpen access · hybridAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in BioMed research international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 30% 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, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Hongjun ZhangDepartment of Ophthalmology, Minhang Hospital, Fudan University, Shanghai, China.
Xiangnan LiuDepartment of Ophthalmology, Changhai Hospital Affiliated to Naval Medical University, Shanghai, China.
Yong'an ChenDepartment of Oncology, Naval Medical Center of Chinese People's Liberation Army, Naval Military Medical University, Shanghai, China.ORCID https://orcid.org/0000-0003-1142-4119
Rui XuDivision of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
Shengli HeDepartment of Hepatobiliary-pancreatic and Integrative Oncology, Minhang Branch, Fudan University Shanghai Cancer Center, 106 Ruili Road, Minhang District, Shanghai, China.ORCID https://orcid.org/0000-0003-0548-2478
Fudan University · CNSecond Military Medical University · CNFudan University Shanghai Cancer Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Uveal Melanoma (UM) is a potentially lethal cancer, and epigenetics may participate in the regulation of MEK resistance. This study is aimed at targeting the epigenetic kinase to overcome the resistance to MEK inhibitor. Method: We developed the 92.1 and OMM1 MEK-inhibitor resistant cell lines by culturing them in the trametinib (Tra) mixed medium. We utilized CCK8 analysis for detecting the viability of the cell. Western blot was used to determine the ERK1/2 and Akt phosphorylation. Small compound library screening assays were carried out by CCK8 analysis. To test the apoptosis, we employed flow cytometric analysis with Annexin-V/PI. Western blot and CCK8 were used to explore the epigenetic regulation of KDM5B in MEK-resistance cell lines. To knock out the expression level of KDM5B, we used the CRISPR/Cas9 by lentivirus delivering well-validated shRNAs in pLKO.1 vector. The directly binding affinity of KDOAM-25 to KDM5B was determined by drug affinity responsive target stability (DARTS) and microscale thermophoresis (MST). Results: The phosphorylation of ERK1/2 and Akt (T308) was inhibited in OMM1 cell lines. However, inhibition of Tra was abolished in OMM1-R cell lines. From a compound screening assay, we identified that KDOAM-25 robustly inhibited the viability and colony formation of MEK-resistance cell lines. Furthermore, KDOAM-25 significantly promoted cell death in OMM1-R cells. H3K4me3 (tri-methylation of lysine 4 on histone H3) and H3K27ac (acetyl of lysine 27 on histone H3) were both upregulated in OMM1-R cells. Tra significantly inhibited the expression of KDM5B in OMM1-P cells. However, the effect on KDM5B was abolished in OMM1-R cells. Knockdown of KDM5B robustly suppressed the cell viability in OMM1-R cells. KDOAM-25 directly interacted with KDM5B. Conclusion: KDOAM-25 inhibited the viability and colony formation and promoted cell death of MEK-resistance cell lines through H3K4me3 and H3K27ac, indicating that KDOAM-25 may be a potential therapeutic agent for MEK resistance in UM patients.

Indexed as

HistonesProto-Oncogene Proteins c-aktAnnexinsCell Line, TumorCell ProliferationEpigenesis, GeneticGlycineHumansJumonji Domain-Containing Histone DemethylasesLysineMelanomaMitogen-Activated Protein Kinase KinasesNiacinamideNuclear ProteinsProtein Kinase InhibitorsRepressor ProteinsAnnexinsGlycineHistonesJumonji Domain-Containing Histone DemethylasesKDM5B protein, humanKDOAM-25LysineMitogen-Activated Protein Kinase KinasesNiacinamideNuclear ProteinsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktRepressor Proteins

Identifiers

PMID36212716
PMCPMC9534647
OpenAlexW4297517277

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.