Acta Biochimica et Biophysica Sinica · 3 authors, 2 centres
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KLF7 is a transcription factor involved in development and diseases, including nervous system development, adipogenesis, and multiple cancers. Genetic polymorphisms in KLF7 are associated with obesity, type 2 diabetes, and mental development, while its expression is dysregulated in cancers such as lung, gastric, and pancreatic cancer. Targeting KLF7 may offer therapeutic potential for neurological damage, metabolic diseases, and cancer.
**Background:** Krüppel-like factor 7 (KLF7) is a zinc-finger transcription factor ubiquitously expressed in adult human tissues. It belongs to the KLF family, which regulates diverse physiological and pathological processes. KLF7 has been implicated in development (nervous system, adipose tissue, muscle, cornea) and diseases such as type 2 diabetes (T2DM), hematologic disorders, and several cancers. This review integrates genetic association, molecular properties, and biological functions of KLF7.
**Methods:** The authors conducted a narrative review of published literature on KLF7, covering genetic studies, molecular biology experiments, and disease-related research. They summarized findings from human genetic association studies, in vitro and in vivo functional analyses, and clinical observations.
**Key Results:** Genetic studies identified SNPs in KLF7 associated with T2DM (rs2302870 in Japanese, OR 1.51 for A vs C), obesity (rs7568369 in Danish, OR 1.09 for C vs A for BMI≥25), and mental development (rs991684 associated with mild mental impairment). DNA methylation of KLF7 is linked to diffuse gastric cancer. KLF7 protein contains an N-terminal acidic domain (aa 1-47) and serine-rich hydrophobic domain (aa 76-211), with a leucine zipper (aa 59-119) for cofactor interaction. It binds CACCC motifs and Sp1 sites. Cofactor MOKA (FBXO38) enhances KLF7 activity. KLF7 regulates nervous system development: KLF7-/- mice die within 2 days, show reduced pain sensitivity, and have defects in olfactory and sensory neurons. KLF7 promotes neurite outgrowth via P21 and P27. In adipose tissue, KLF7 is highly expressed in preadipocytes and inhibits differentiation; overexpression reduces adiponectin and leptin secretion. In muscle, KLF7 maintains satellite cell quiescence. In cornea, KLF7 tempers proliferation and represses differentiation. KLF7 is upregulated in lung adenocarcinoma (associated with larger tumor size, lymph node metastasis, poor survival), gastric cancer (promotes migration), head and neck squamous cell carcinoma (induces EMT via SNAIL), pancreatic ductal adenocarcinoma (promotes invasion), glioma (activates urea cycle via ASL), and ovarian cancer. Chemical substances like morphine upregulate KLF7, while (-)-catechin and pitavastatin downregulate it.
**Clinical Implications:** KLF7 is a potential therapeutic target for neurological injuries (overexpression promotes regeneration), metabolic diseases (inhibition may improve insulin sensitivity and adipokine profile), and cancers (downregulation may suppress tumor progression). SNPs in KLF7 may serve as biomarkers for obesity and T2DM risk. DNA methylation of KLF7 could be a marker for diffuse gastric cancer. Drugs like trametinib (MEK inhibitor) and pitavastatin may exert effects partly through KLF7 modulation. Further research is needed to clarify KLF7 protein structure and in vivo functions.