Tumor suppressor candidate 2 (TUSC2) mRNA 3′-untranslated region (TUSC2 mRNA 3′-UTR)

The FUS-1 mRNA 3′-untranslated region (3′-UTR) is a key regulatory element of the Tumor Suppressor Candidate 2 (TUSC2) transcript, which was historically designated as FUS1 (PMID: 20350355). This region is essential for the post-transcriptional control of TUSC2, a potent tumor suppressor located in the 3p21.3 chromosomal region that is frequently deleted in non-small cell lung cancer and other malignancies (PMID: 19638417). The 3′-UTR contains highly conserved binding sites for several oncogenic microRNAs, including miR-93, miR-98, miR-197, and miR-378, which negatively regulate TUSC2 expression by inducing mRNA degradation or translational repression (PMID: 17984053). In cancer cells, the overexpression of these microRNAs leads to the silencing of TUSC2, thereby facilitating tumor progression, evasion of apoptosis, and angiogenesis. Therapeutic interventions targeting this pathway include gene replacement therapies like REQORSA (GPX-001), which delivers a functional TUSC2 gene to bypass endogenous repression. Additionally, the 3′-UTR of the FUS (Fused in Sarcoma) gene is a significant site for mutations in amyotrophic lateral sclerosis (ALS), where it contributes to the toxic overexpression of the FUS protein (PMID: 25004804). Antisense oligonucleotides such as ION363 (ulefnersen) are currently in clinical development to target the FUS mRNA and reduce the burden of these pathogenic protein aggregates (PMID: 35075293).

Other names

FUS1 mRNA 3′-UTRFUS-1 3′-UTRTUSC2 3′-UTRTumor suppressor candidate 2 3′-untranslated regionFused in sarcoma (FUS) mRNA 3′-UTR

Restoration of tumor suppressor expression via gene replacement; Antisense-mediated degradation of mRNA to reduce toxic protein levels; Competitive inhibition of microRNA binding to regulatory elements.