Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer.
Antagomirs
/ genetics
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Chemotherapy, Adjuvant
/ methods
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
MicroRNAs
/ agonists
Neoplasms
/ genetics
Oligoribonucleotides
/ genetics
RNA Stability
RNA, Messenger
/ genetics
RNA, Neoplasm
/ agonists
Small Molecule Libraries
/ therapeutic use
Systems Biology
/ methods
Tumor Suppressor Proteins
/ agonists
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
05 09 2019
05 09 2019
Historique:
accepted:
13
07
2019
revised:
05
07
2019
received:
08
05
2019
pubmed:
25
7
2019
medline:
4
12
2019
entrez:
25
7
2019
Statut:
ppublish
Résumé
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by suppressing mRNA translation and reducing mRNA stability. A miRNA can potentially bind many mRNAs, thereby affecting the expression of oncogenes and tumor suppressor genes as well as the activity of whole pathways. The promise of miRNA therapeutics in cancer is to harness this evolutionarily conserved mechanism for the coordinated regulation of gene expression, and thus restoring a normal cell phenotype. However, the promiscuous binding of miRNAs can provoke unwanted off-target effects, which are usually caused by high-dose single-miRNA treatments. Thus, it is desirable to develop miRNA therapeutics with increased specificity and efficacy. To achieve that, we propose the concept of miRNA cooperativity in order to exert synergistic repression on target genes, thus lowering the required total amount of miRNAs. We first review miRNA therapies in clinical application. Next, we summarize the knowledge on the molecular mechanism and biological function of miRNA cooperativity and discuss its application in cancer therapies. We then propose and discuss a systems biology approach to investigate miRNA cooperativity for the clinical setting. Altogether, we point out the potential of miRNA cooperativity to reduce off-target effects and to complement conventional, targeted, or immune-based therapies for cancer.
Identifiants
pubmed: 31340025
pii: 5538016
doi: 10.1093/nar/gkz638
pmc: PMC6735922
doi:
Substances chimiques
Antagomirs
0
Antineoplastic Agents
0
MicroRNAs
0
Oligoribonucleotides
0
RNA, Messenger
0
RNA, Neoplasm
0
Small Molecule Libraries
0
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
7753-7766Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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