Evidence map›Paper›PMID 27328938›Full record

ArticleJournal of nanobiotechnology2016

Folate receptor-targeted nanoparticle delivery of HuR-RNAi suppresses lung cancer cell proliferation and migration.

Ranganayaki Muralidharan, Anish Babu, Narsireddy Amreddy, Kanthesh Basalingappa, Meghna Mehta, Allshine Chen, Yan Daniel Zhao, Uday B Kompella, Anupama Munshi, Rajagopal Ramesh

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

Article in Journal of nanobiotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 95 citations in OpenAlex.

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  17. Pharmacokinetics and tumor delivery of nanoparticles.Journal of drug delivery science and technology · 2023
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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.

Ranganayaki MuralidharanDepartments of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Anish BabuDepartments of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Narsireddy AmreddyDepartments of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Kanthesh BasalingappaDepartments of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Meghna MehtaDepartments of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Allshine ChenDepartments of Epidemiology and Statistics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Yan Daniel ZhaoDepartments of Epidemiology and Statistics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Uday B KompellaDepartment of Pharmaceutical Sciences and Opthalmology, University of Colorado, Denver, CO, 80045, USA.
Anupama MunshiDepartments of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Rajagopal RameshDepartments of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. rajagopal-ramesh@ouhsc.edu.ORCID http://orcid.org/0000-0002-7658-5338
University of Oklahoma Health Sciences Center · USOklahoma City University · USUniversity of Colorado Denver · US

Funding

TUMOR RESISTANCE MECHANISMS TO ANTI-VEGF THERAPY IN PROSTATE CANCER (Sukyung Woo)P20GM103639 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI DHANASEKARAN, DANNY N. · 2012 to 2022
$21.3M
HuR Targeted Nanotherapy for Lung CancerR01CA167516 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI RAMESH, RAJAGOPAL · 2013 to 2017
$1.9M
NCI NIH HHS R01 CA167516NIGMS NIH HHS P20 GM103639
6 · The paper itself

Abstract

backgroundHuman antigen R (HuR) is an RNA binding protein that is overexpressed in many human cancers, including lung cancer, and has been shown to regulate the expression of several oncoproteins. Further, HuR overexpression in cancer cells has been associated with poor-prognosis and therapy resistance. Therefore, we hypothesized that targeted inhibition of HuR in cancer cells should suppress several HuR-regulated oncoproteins resulting in an effective anticancer efficacy. To test our hypothesis, in the present study we investigated the efficacy of folate receptor-α (FRA)-targeted DOTAP:Cholesterol lipid nanoparticles carrying HuR siRNA (HuR-FNP) against human lung cancer cells.

resultsThe therapeutic efficacy of HuR-FNP was tested in FRA overexpressing human H1299 lung cancer cell line and compared to normal lung fibroblast (CCD16) cells that had low to no FRA expression. Physico-chemical characterization studies showed HuR-FNP particle size was 303.3 nm in diameter and had a positive surface charge (+4.3 mV). Gel retardation and serum stability assays showed that the FNPs were efficiently protected siRNA from rapid degradation. FNP uptake was significantly higher in H1299 cells compared to CCD16 cells indicating a receptor-dose effect. The results of competitive inhibition studies in H1299 cells demonstrated that HuR-FNPs were efficiently internalized via FRA-mediated endocytosis. Biologic studies demonstrated HuR-FNP but not C-FNP (control siRNA) induced G1 phase cell-cycle arrest and apoptosis in H1299 cells resulting in significant growth inhibition. Further, HuR-FNP exhibited significantly higher cytotoxicity against H1299 cells than it did against CCD16 cells. The reduction in H1299 cell viability was correlated with a marked decrease in HuR mRNA and protein expression. Further, reduced expression of HuR-regulated oncoproteins (cyclin D1, cyclin E, and Bcl-2) and increased p27 tumor suppressor protein were observed in HuR-FNP-treated H1299 cells but not in C-FNP-treated cells. Finally, cell migration was significantly inhibited in HuR-FNP-treated H1299 cells compared to C-FNP.

conclusionsOur results demonstrate that HuR is a molecular target for lung cancer therapy and its suppression using HuR-FNP produced significant therapeutic efficacy in vitro.

Indexed as

RNAi TherapeuticsCell Line, TumorCell MovementCell ProliferationCholesterolDrug Delivery SystemsELAV-Like Protein 1Folate Receptor 1Folic AcidGene Expression Regulation, NeoplasticHumansLungLung NeoplasmsNanoparticlesRNA, Small InterferingCholesterolELAVL1 protein, humanELAV-Like Protein 1Folate Receptor 1Folic AcidRNA, Small InterferingFolateHuRLung cancerNanoparticleOncoproteinsiRNATargeting

Identifiers

PMID27328938
PMCPMC4915183
OpenAlexW2472500434

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.