Target intelligence / Profile preview

SMAD family member 7 mRNA 3'-untranslated region (Smad7 mRNA 3'-UTR)

Target
Smad7 mRNA 3'-UTR
Molecular classification
Nucleic acid, Messenger RNA (mRNA) regulatory region
01

Overview

The Smad7 mRNA 3'-untranslated region (3'-UTR) is a critical regulatory segment of the transcript encoding the inhibitory Smad7 protein. Smad7 is a key negative regulator of the Transforming Growth Factor-beta (TGF-beta) and Bone Morphogenetic Protein (BMP) signaling pathways, acting by blocking receptor-mediated phosphorylation of R-Smads and promoting receptor degradation. The 3'-UTR serves as a major hub for post-transcriptional control, containing multiple binding sites for microRNAs (miRNAs) such as miR-21, miR-15, and miR-195, which repress Smad7 expression. Dysregulation of this region or its associated miRNAs is linked to various pathologies, including Crohn's disease, where Smad7 overexpression inhibits anti-inflammatory TGF-beta signaling, and several cancers where Smad7 levels influence tumor progression and metastasis. Consequently, the Smad7 mRNA 3'-UTR is an important target for RNA-based therapeutics, such as miRNA mimics or antisense oligonucleotides, designed to modulate Smad7 levels and restore signaling homeostasis.

Other names
Mothers against decapentaplegic homolog 7 mRNA 3'-UTRSMAD7 3'-UTRMADH7 mRNA 3'-UTRSmad7 3'-untranslated region
02

Mechanism of action

Binding of microRNAs or antisense oligonucleotides to the 3'-UTR sequence leads to translational repression or mRNA degradation, thereby modulating Smad7 protein levels and downstream TGF-beta/BMP signaling pathways.

03

Biological functions

Post-transcriptional regulation of gene expressionMicroRNA binding siteNegative regulation of TGF-beta signalingNegative regulation of BMP signalingRegulation of mRNA stability
04

Disease associations

Crohn's diseaseInflammatory bowel diseaseFibrosis (liver, lung, renal)Colorectal cancerBreast cancerPancreatic cancerDiabetic nephropathyKeloid formation
05

Safety considerations

Off-target effects of microRNA-based therapeuticsPotential for excessive TGF-beta signaling leading to tissue fibrosisImmune system activation by synthetic oligonucleotidesDelivery challenges to specific target tissues such as the intestinal mucosa
06

Interacting drugs

MicroRNA-21 mimics

5 more in the full profile.

07

Biomarkers

Smad7 mRNA expression levelsMicroRNA-21 expression levelsPhosphorylated Smad2/3 (p-Smad2/3) levelsTGF-beta1 signaling activity

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