Genetic variations and functions of KLF14 in gene expression and metabolic disease development

Krüppel-like factor 14 (KLF14) is a pivotal trans-regulatory transcription factor that modulates diverse biological processes, including insulin sensitivity, glucose homeostasis, lipid metabolism, and potentially cancer suppression through its regulation of centrosome amplification and apoptosis in colorectal cancer cells. KLF14 has been associated with the pathogenesis of metabolic disorders, including obesity, insulin resistance, and type 2 diabetes (T2D), and contains CpG sites that exhibit age-associated methylation changes, which may serve as potential biomarkers for estimating an individual age. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are significantly associated with KLF14 expression in adipose tissue. The functional impact of KLF14 is influenced by both physiological and environmental factors, underscoring its complex role in disease pathogenesis. Population-based genetic studies reveal significant interethnic variability in KLF14 polymorphisms, highlighting the necessity of incorporating ethnic diversity into genetic research. Moreover, a deeper understanding of the molecular regulatory mechanisms and disease associations of KLF14 could inform the development of targeted therapies and personalized medicine strategies. Thus, the current study underscores the significance of KLF14 as a trans-regulatory gene and a potential therapeutic target, emphasizing its intricate role in biological regulation and disease pathogenesis.