Forkhead box protein O1 mRNA (FOXO1 mRNA)

Forkhead box protein O1 (FOXO1) mRNA is the transcript encoding a critical transcription factor that serves as a central regulator of metabolic homeostasis and cellular fate (UniProt P12757). In the liver, FOXO1 drives the expression of key gluconeogenic genes such as G6PC and PCK1, and its overactivity is a major contributor to the fasting hyperglycemia observed in type 2 diabetes (PubMed: 21832139). Consequently, FOXO1 mRNA has emerged as a therapeutic target for antisense oligonucleotides (ASOs), such as IONIS-FOXO1Rx, which aim to reduce hepatic glucose production by promoting the degradation of the FOXO1 transcript (ClinicalTrials.gov: NCT01808352). In addition to its metabolic role, FOXO1 functions as a tumor suppressor in various tissues by inducing cell cycle arrest and apoptosis; however, its chromosomal translocation to form the PAX3-FOXO1 fusion protein is a hallmark of alveolar rhabdomyosarcoma (PubMed: 15254671). The therapeutic modulation of FOXO1 mRNA requires careful calibration to avoid systemic side effects, such as hypoglycemia or the unintended promotion of oncogenesis in tissues where FOXO1 maintains genomic stability.

Other names

FKHRFOXO1AForkhead in rhabdomyosarcomaFKH1

Antisense oligonucleotide-mediated mRNA degradation