Target intelligence / Profile preview

Proliferating cell nuclear antigen (PCNA) messenger RNA 3' untranslated region (PCNA mRNA 3'UTR)

Target
PCNA mRNA 3'UTR
Molecular classification
Messenger RNA, Untranslated region, RNA
01

Overview

The Proliferating cell nuclear antigen (PCNA) messenger RNA 3' untranslated region (3'UTR) is a critical regulatory segment of the PCNA transcript that governs mRNA stability and translation efficiency (PubMed: 10854306). PCNA itself functions as a DNA clamp and a processivity factor for DNA polymerase delta, making it indispensable for DNA replication and various DNA repair pathways (UniProt: P12004). In many cancers, PCNA is significantly overexpressed to support rapid cell proliferation, making its mRNA a viable therapeutic target (PubMed: 25635393). Antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) designed to bind the PCNA mRNA 3'UTR can trigger the degradation of the transcript or physically block the translation machinery (PubMed: 15103328). This reduction in PCNA protein levels disrupts the replication fork and induces cell cycle arrest and apoptosis in malignant cells. While targeting the 3'UTR offers a strategy to downregulate this essential protein, challenges include ensuring tumor-specific delivery and minimizing effects on healthy, rapidly dividing cells (PubMed: 19029616).

Other names
PCNA 3'UTRProliferating cell nuclear antigen 3' untranslated regionPCNA mRNA 3-prime untranslated region
02

Mechanism of action

Antisense-mediated mRNA degradation (RNase H-dependent) or translational inhibition, leading to reduced PCNA protein expression and subsequent inhibition of DNA replication and repair.

03

Biological functions

Regulation of mRNA stabilityRegulation of translationDNA replicationDNA repairCell cycle regulation
04

Disease associations

CancerSolid tumorsBreast cancerProstate cancer
05

Safety considerations

Off-target RNA bindingPotential toxicity to normal proliferating tissues (e.g., bone marrow, GI tract)Delivery efficiency to tumor sites
06

Interacting drugs

AON-PCNA

1 more in the full profile.

07

Biomarkers

PCNA protein expression levelsKi-67 proliferation indexApoptotic markers (e.g., Cleaved Caspase-3)

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