Evidence map›Paper›PMID 31546954›Full record

ArticleCells2019

Proteomic Analysis of miR-195 and miR-497 Replacement Reveals Potential Candidates that Increase Sensitivity to Oxaliplatin in MSI/P53wt Colorectal Cancer Cells.

Dennis Poel, Lenka N C Boyd, Robin Beekhof, Tim Schelfhorst, Thang V Pham, Sander R Piersma, Jaco C Knol, Connie R Jimenez, Henk M W Verheul, Tineke E Buffart

Open access · goldAbstract read
In one paragraph

Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

16 citing papers in PubMed, 30 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

10 authors at 3 institutions in 1 country.

Dennis PoelDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. dennis.poel@radboudumc.nl.ORCID 0000-0002-4395-2824
Lenka N C BoydDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands.
Robin BeekhofDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. r.beekhof@amsterdamumc.nl.ORCID 0000-0002-9500-528X
Tim SchelfhorstDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. t.schelfhorst@nki.nl.ORCID 0000-0003-3444-0971
Thang V PhamDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. t.pham@amsterdamumc.nl.
Sander R PiersmaDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. s.piersma@amsterdamumc.nl.ORCID 0000-0001-7262-3395
Jaco C KnolDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. j.knol@amsterdamumc.nl.
Connie R JimenezDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. c.jimenez@amsterdamumc.nl.
Henk M W VerheulDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands.
Tineke E BuffartDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081HV Amsterdam, The Netherlands. t.buffart@nki.nl.
Amsterdam UMC Location Vrije Universiteit Amsterdam · NLRadboud University Nijmegen · NLThe Netherlands Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most patients with advanced colorectal cancer (CRC) eventually develop resistance to systemic combination therapy. miR-195-5p and miR-497-5p are downregulated in CRC tissues and associated with drug resistance. Sensitization to 5-FU, oxaliplatin, and irinotecan by transfection with miR-195-5p and miR-497-5p mimics was studied using cell viability and clonogenic assays in cell lines HCT116, RKO, DLD-1, and SW480. In addition, proteomic analysis of transfected cells was implemented to identify potential targets. Significantly altered proteins were subjected to STRING (protein-protein interaction networks) database analysis to study the potential mechanisms of drug resistance. Cell viability analysis of transfected cells revealed increased sensitivity to oxaliplatin in microsatellite instable (MSI)/P53 wild-type HCT116 and RKO cells. HCT116 transfected cells formed significantly fewer colonies when treated with oxaliplatin. In sensitized cells, proteomic analysis showed 158 and 202 proteins with significantly altered expression after transfection with miR-195-5p and miR-497-5p mimics respectively, of which CHUK and LUZP1 proved to be coinciding downregulated proteins. Resistance mechanisms of these proteins may be associated with nuclear factor kappa-B signaling and G1 cell-cycle arrest. In conclusion, miR-195-5p and miR-497-5p replacement enhanced sensitivity to oxaliplatin in treatment naïve MSI/P53 wild-type CRC cells. Proteomic analysis revealed potential miRNA targets associated with the cell-cycle which possibly bare a relation with chemotherapy sensitivity.

Indexed as

Antineoplastic AgentsCell ProliferationCell SurvivalColorectal NeoplasmsHCT116 CellsHumansMicroRNAsMicrosatellite InstabilityOxaliplatinProteomicsRNA, MessengerTumor Cells, CulturedTumor Suppressor Protein p53Antineoplastic AgentsMicroRNAsMIRN195 microRNA, humanMIRN497 microRNA, humanOxaliplatinRNA, MessengerTumor Suppressor Protein p53chemotherapycolorectal cancermicroRNAproteomics

Identifiers

PMID31546954
PMCPMC6770888
OpenAlexW2974653596

What OpenQuestion holds

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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.