Evidence map›Paper›PMID 33763422›Full record

ReviewFrontiers in cell and developmental biology2021

MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic.

Wen Jess Li, Yunfei Wang, Ruifang Liu, Andrea L Kasinski, Haifa Shen, Frank J Slack, Dean G Tang

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 2 pooled it
9.9field-weighted citation impact, top 1% 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

122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.

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  6. Systemic Molecular Alterations ofInternational journal of molecular sciences · 2026
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62 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 2 countries.

Wen Jess LiDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Yunfei WangDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Ruifang LiuDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Andrea L KasinskiDepartment of Biological Sciences, Purdue University, West Lafayette, IN, United States.
Haifa ShenDepartment of Nanomedicine, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, United States.
Frank J SlackDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Dean G TangDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Roswell Park Comprehensive Cancer Center · USHarvard University · USMethodist Hospital · USPurdue University West Lafayette · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI CANDACE S JOHNSON · 1985 to 2026
$116.6M
Precision microRNA medicine in cancerR35CA232105 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SLACK, FRANK J. · 2019 to 2025
$7.2M
Ligand-mediated, vehicle-free delivery of small RNAsR01CA226259 · NCI · PURDUE UNIVERSITY · PI Andrea L Kasinski · 2018 to 2026
$3.4M
Novel Therapeutic Strategies to Co-Target Undifferentiated Prostate Cancer (PCa) Stem Cells and Bulk PCa CellsR01CA240290 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 2019 to 2026
$3.1M
Enhancing miRNA Therapeutics through Vehicle Free DeliveryR01CA205420 · NCI · PURDUE UNIVERSITY · PI Andrea L Kasinski · 2017 to 2026
$2.9M
Mechanism of Intratumoral Transport of Particulate DrugsR01CA222959 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHEN, SHU-HSIA, LIU, XUEWU · 2018 to 2023
$2.3M
Tumor-Suppressive Functions and Molecular Regulation of LRIG1 in Prostate Cancer and CRPCR01CA237027 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI TANG, DEAN G. · 2019 to 2023
$2.2M
Correlative efficacy, biomarker, and mechanistic studies associated with a phase Ib/II clinical trial of treating mCRPC patients with enzalutamide and VenetoclaxR21CA237939 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI TANG, DEAN G. · 2020 to 2021
$449k
Slow-cycling cells, therapy resistance and clinical implications in prostate cancerR21CA218635 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI TANG, DEAN G. · 2018 to 2019
$404k
NCI NIH HHS P30 CA016056NCI NIH HHS R01 CA205420NCI NIH HHS R01 CA222959NCI NIH HHS R01 CA226259NCI NIH HHS R01 CA237027NCI NIH HHS R01 CA240290NCI NIH HHS R21 CA218635NCI NIH HHS R21 CA237939NCI NIH HHS R35 CA232105
6 · The paper itself

Abstract

Overwhelming evidence indicates that virtually all treatment-naive tumors contain a subpopulation of cancer cells that possess some stem cell traits and properties and are operationally defined as cancer cell stem cells (CSCs). CSCs manifest inherent heterogeneity in that they may exist in an epithelial and proliferative state or a mesenchymal non-proliferative and invasive state. Spontaneous tumor progression, therapeutic treatments, and (epi)genetic mutations may also induce plasticity in non-CSCs and reprogram them into stem-like cancer cells. Intrinsic cancer cell heterogeneity and induced cancer cell plasticity, constantly and dynamically, generate a pool of CSC subpopulations with varying levels of epigenomic stability and stemness. Despite the dynamic and transient nature of CSCs, they play fundamental roles in mediating therapy resistance and tumor relapse. It is now clear that the stemness of CSCs is coordinately regulated by genetic factors and epigenetic mechanisms. Here, in this perspective, we first provide a brief updated overview of CSCs. We then focus on microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA) devoid in many CSCs and advanced tumors. Being a member of the miR-34 family, miR-34a was identified as a p53 target in 2007. It is a bona fide tumor suppressor, and its expression is dysregulated and downregulated in various human cancers. By targeting stemness factors such as NOTCH, MYC, BCL-2, and CD44, miR-34a epigenetically and negatively regulates the functional properties of CSCs. We shall briefly discuss potential reasons behind the failure of the first-in-class clinical trial of MRX34, a liposomal miR-34a mimic. Finally, we offer several clinical settings where miR-34a can potentially be deployed to therapeutically target CSCs and advanced, therapy-resistant, and p53-mutant tumors in order to overcome therapy resistance and curb tumor relapse.

Indexed as

cancer cell heterogeneitycancer stem cellsmicroRNAmiR-34amiRNA therapeutics

Identifiers

PMID33763422
PMCPMC7982597
OpenAlexW3135601979

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.