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Multiple mRNA targets bearing miR-X miRNA response elements (miR-X targets)

Target
miR-X targets
Molecular classification
Messenger RNA, Nucleic acid
01

Overview

The target "Multiple mRNA targets bearing miR-X miRNA response elements" refers to a collective set of messenger RNA (mRNA) molecules that are post-transcriptionally regulated by a specific microRNA, denoted here by the placeholder "miR-X". These mRNAs contain specific sequences known as miRNA response elements (MREs), typically located in their 3' untranslated regions (UTRs), which serve as binding sites for the miRNA-guided RNA-induced silencing complex (RISC) (Bartel, Cell, 2009). The binding of the miRNA to these MREs results in either the degradation of the mRNA transcript or the repression of its translation into protein, thereby silencing gene expression (Gebert & MacRae, Nature Reviews Molecular Cell Biology, 2019). In a therapeutic context, this target represents a regulatory network where a single drug, such as a miRNA mimic or an antagomir, can simultaneously modulate multiple genes involved in a disease pathway (Rupaimoole & Slack, Nature Reviews Drug Discovery, 2017). miRNA mimics are designed to enhance the silencing of these targets, while antagomirs block the miRNA to restore target protein levels. This approach is particularly relevant in complex diseases like cancer, where multiple oncogenic mRNAs may be regulated by a single tumor-suppressive miRNA. However, the use of "miR-X" indicates that the specific miRNA and its associated mRNA targets must be defined for clinical application, and the broad nature of miRNA targeting poses significant challenges regarding off-target effects and systemic toxicity.

Other names
miRNA response elementsMRE-containing mRNAsmicroRNA targetsmiR-X regulated transcriptsmiRNA-target gene network
02

Mechanism of action

Drugs modulate the expression of these mRNA targets by either supplementing the inhibitory effect of a miRNA (mimics) or blocking the miRNA from binding to its response elements (antagomirs), thereby altering protein synthesis through the RNA-induced silencing complex (RISC) pathway.

03

Biological functions

Post-transcriptional gene regulationGene silencingmRNA degradationTranslational inhibitionRNA interference
04

Disease associations

CancerCardiovascular diseaseInfectionMetabolic disorderNeurodegenerative disease
05

Safety considerations

Off-target effects on unintended mRNAsSaturation of the endogenous RNAi machineryInnate immune activation via TLR7/8Unintended downregulation of essential genes within the miRNA networkSystemic toxicity from multi-gene modulation
06

Interacting drugs

miRNA mimics

4 more in the full profile.

07

Biomarkers

miRNA expression levelsTarget mRNA expression levelsDownstream protein expressionRISC complex activity

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