Evidence map›Paper›PMID 37357618›Full record

ArticleMolecular oncology2023

Functional inhibition of the RNA-binding protein HuR sensitizes triple-negative breast cancer to chemotherapy.

Lanjing Wei, Qi Zhang, Cuncong Zhong, Lily He, Yuxia Zhang, Ahlam M Armaly, Jeffrey Aubé, Danny R Welch, Liang Xu, Xiaoqing Wu

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2023. 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
2.6field-weighted citation impact, top 10% 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, 17 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 4 institutions in 1 country.

Lanjing WeiBioengineering Program, The University of Kansas, Lawrence, KS, USA.ORCID 0000-0001-9170-0931
Qi ZhangDepartment of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.
Cuncong ZhongDepartment of Electrical Engineering and Computer Science, The University of Kansas, Lawrence, KS, USA.
Lily HeDepartment of Pharmacology, Toxicology & Therapeutics, The University of Kansas Medical Center, Kansas City, KS, USA.
Yuxia ZhangDepartment of Pharmacology, Toxicology & Therapeutics, The University of Kansas Medical Center, Kansas City, KS, USA.
Ahlam M ArmalyDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
Jeffrey AubéDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
Danny R WelchDepartment of Cancer Biology, The University of Kansas Medical Center, Kansas City, KS, USA.
Liang XuDepartment of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.ORCID 0000-0001-9196-4232
Xiaoqing WuThe University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0003-2076-4107
University of Kansas · USUniversity of Kansas Medical Center · USUniversity of North Carolina at Chapel Hill · USThe University of Kansas Cancer Center · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Transgenic & Gene-Targeting Shared ResourceP30CA168524 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ROY A. JENSEN · 2012 to 2026
$40.1M
Nano-Engineered Lab-on-a-Chip for Assessing HuR-Regulated Exosomes for Cancer Monitoring and Targeted TherapyR01CA243445 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI DIXON, DAN ALAN, XU, LIANG · 2019 to 2023
$3.0M
Molecular cancer therapy targeting HuR-ARE interactionR01CA191785 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI AUBE, JEFFREY, XU, LIANG · 2015 to 2019
$2.1M
RNA-binding protein HuR in liver pathophysiology and carcinogenesisR01DK119131 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ZHANG, YUXIA · 2019 to 2023
$1.8M
NCI NIH HHS P30 CA016086NCI NIH HHS P30 CA168524NCI NIH HHS R01 CA191785NCI NIH HHS R01 CA243445NIDDK NIH HHS R01 DK119131NIH HHS CA243445NIH HHS DK119131NIH HHS P30 CA168524NIH HHS R01 CA191785
6 · The paper itself

Abstract

Chemotherapy remains the standard treatment for triple-negative breast cancer (TNBC); however, chemoresistance compromises its efficacy. The RNA-binding protein Hu antigen R (HuR) could be a potential therapeutic target to enhance the chemotherapy efficacy. HuR is known to mainly stabilize its target mRNAs, and/or promote the translation of encoded proteins, which are implicated in multiple cancer hallmarks, including chemoresistance. In this study, a docetaxel-resistant cell subline (231-TR) was established from the human TNBC cell line MDA-MB-231. Both the parental and resistant cell lines exhibited similar sensitivity to the small molecule functional inhibitor of HuR, KH-3. Docetaxel and KH-3 combination therapy synergistically inhibited cell proliferation in TNBC cells and tumor growth in three animal models. KH-3 downregulated the expression levels of HuR targets (e.g., β-Catenin and BCL2) in a time- and dose-dependent manner. Moreover, KH-3 restored docetaxel's effects on activating Caspase-3 and cleaving PARP in 231-TR cells, induced apoptotic cell death, and caused S-phase cell cycle arrest. Together, our findings suggest that HuR is a critical mediator of docetaxel resistance and provide a rationale for combining HuR inhibitors and chemotherapeutic agents to enhance chemotherapy efficacy.

Indexed as

Triple Negative Breast NeoplasmsAnimalsApoptosisCell Line, TumorCell ProliferationDocetaxelELAV-Like Protein 1HumansRNA-Binding ProteinsDocetaxelELAVL1 protein, humanELAV-Like Protein 1RNA-Binding Proteinsanimal tumor modelchemoresistancedocetaxelHuRTNBC

Identifiers

PMID37357618
PMCPMC10552894
OpenAlexW4382011332

What OpenQuestion holds

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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.