Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer

Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Nucleic Acids Research
Volume: 47
Number: 15
Page Range: pp. 7753-7766
Date: 2019
Divisions: Computational BioMedicine
Depositing User: General Admin
Identification Number: 10.1093/nar/gkz638
ISSN: 0305-1048
Date Deposited: 21 Dec 2020 23:18

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.

© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

Lai, Xin
Eberhardt, Martin
Schmitz, Ulf
Vera, Julio
Last Modified: 21 Dec 2020 23:18

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