Evidence map›Paper›PMID 25846727›Full record

ArticleThe Journal of surgical research2015

p85α is a microRNA target and affects chemosensitivity in pancreatic cancer.

Paul A Toste, Luyi Li, Brian E Kadera, Andrew H Nguyen, Linh M Tran, Nanping Wu, David L Madnick, Sanjeet G Patel, David W Dawson, Timothy R Donahue

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of surgical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
1.9field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.

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  15. Emerging Role of MicroRNAs in mTOR Signaling.Cellular and molecular life sciences : CMLS · 2017
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  19. Article
  20. Noncoding RNAs and pancreatic cancer.World journal of gastroenterology · 2016
    Review
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 1 institution in 1 country.

Paul A Toste *Department of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Luyi Li *Department of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Brian E KaderaDepartment of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Andrew H NguyenDepartment of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Linh M TranDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Nanping WuDepartment of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
David L MadnickDepartment of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Sanjeet G PatelDepartment of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
David W DawsonDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Timothy R DonahueDepartment of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
University of California, Los Angeles · US

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Targeting diet-induced promotion of Kras-initiated pancreatic adenocarcinomaP01CA163200 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PANDOL, STEPHEN J. · 2012 to 2016
$6.2M
PET Imaging-guided Personalized Therapy in Pancreatic CancerR01CA187678 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CZERNIN, JOHANNES, DONAHUE, TIMOTHY R · 2014 to 2018
$2.8M
NCI NIH HHS L30 CA151241NCI NIH HHS R01 CA187678NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P30DK41301
6 · The paper itself

Abstract

backgroundWe previously identified a correlation between increased expression of the phosphoinositide 3-kinase (PI3K) regulatory subunit p85α and improved survival in human pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the impact of changes in p85α expression on response to chemotherapy and the regulation of p85α by microRNA-21 (miR-21). MATERIALS AND

methodsPDAC tumor cells overexpressing p85α were generated by viral transduction, and the effect of p85α overexpression on sensitivity to gemcitabine was tested by MTT assay. Primary human PDAC tumors were stained for p85α and miR-21 via immunohistochemistry and in situ hybridization, respectively. Additionally, PDAC cells were treated with miR-21 mimic, and changes in p85α and phospho-AKT were assessed by Western blot. Finally, a luciferase reporter assay system was used to test direct regulation of p85α by miR-21.

resultsHigher p85α expression resulted in increased sensitivity to gemcitabine (P < 0.01), which correlated with decreased PI3K-AKT activation. Human tumors demonstrated an inverse correlation between miR-21 and p85α expression levels (r = -0.353, P < 0.001). In vitro, overexpression of miR-21 resulted in decreased levels of p85α and increased phosphorylation of AKT. Luciferase reporter assays confirmed the direct regulation of p85α by miR-21 (P < 0.01).

conclusionsOur results demonstrate that p85α expression is a determinant of chemosensitivity in PDAC. Additionally, we provide novel evidence that miR-21 can influence PI3K-AKT signaling via its direct regulation of p85α. These data provide insight into potential mechanisms for the known relationship between increased p85α expression and improved survival in PDAC.

Indexed as

Antimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalCell Line, TumorClass Ia Phosphatidylinositol 3-KinaseDeoxycytidineGemcitabineHEK293 CellsHumansMicroRNAsPancreatic NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAntimetabolites, AntineoplasticClass Ia Phosphatidylinositol 3-KinaseDeoxycytidineGemcitabineMicroRNAsMIRN21 microRNA, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktChemoresistancemiR-21p85αPancreatic cancerPIK3R1

Identifiers

PMID25846727
PMCPMC4442711
OpenAlexW2163279259

What OpenQuestion holds

Textmetadata
LicenceTDM
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.