The Rbm38-p63 feedback loop is critical for tumor suppression and longevity

Area of Science:

• Molecular Biology
• Genetics
• Aging Research

Background:

• The RNA-binding protein Rbm38 targets the p63 tumor suppressor, forming a negative feedback loop by repressing p63 expression.
• Understanding the in vivo significance of this Rbm38-p63 loop is crucial for aging and tumorigenesis research.

Purpose of the Study:

• To investigate the biological role of the Rbm38-p63 feedback loop in vivo.
• To assess the impact of Rbm38 and p63 deficiency on lifespan, tumor incidence, and aging phenotypes.

Main Methods:

• Generation and lifespan monitoring of wild-type, Rbm38 knockout, TAp63 heterozygous, and compound Rbm38 knockout;TAp63 heterozygous mice.
• Assessment of tumor incidence, liver steatosis, cellular senescence markers, and inflammatory cytokine levels (IL17D, Tnfsf15).

Main Results:

• Compound Rbm38^-/-;TAp63^+/- mice exhibited extended lifespan and reduced tumor incidence compared to single-deficient mice.
• Rbm38 deficiency decreased liver steatosis and reduced senescence biomarkers in TAp63^+/- mice.
• Rbm38 deficiency conferred resistance to cellular senescence and lowered inflammatory cytokine levels in mouse livers and MEFs.

Conclusions:

• Rbm38 and p63 act as intergenic suppressors of aging and tumorigenesis.
• The Rbm38-p63 feedback loop presents a potential target for interventions aimed at enhancing longevity and managing cancer.