Klf3-KO Mouse

Klf3, also known as Kruppel-like factor 3 (basic), is a transcription factor involved in multiple biological processes. It plays a role in adipogenesis as a negative regulator, and is associated with pathways like autophagy, WNT/β-catenin, and insulin signaling. It also has implications in cell differentiation and development, making it biologically important. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable for studying its functions [1-4].

In adipogenesis, Garcinia cambogia was found to elevate Klf3 expression by reducing SQSTM1/p62-mediated selective autophagic degradation, which in turn inhibited Cebpa and Pparg transcription, attenuating adipogenesis [1]. In colorectal cancer, silencing Klf3 increased cell proliferation, migration, and invasion, while activation decreased these processes, and downregulated Klf3 was associated with accelerated tumor growth in vivo, with Klf3 targeting the promoter sequence of WNT1 [2]. In skeletal muscle, knockdown of Klf3 promoted basal and insulin-stimulated glucose uptake in L6 myotubes, while overexpression had the opposite effect, affecting insulin-related pathways [3]. In epidermal differentiation, knockdown of Klf3 led to reduced differentiation gene expression, and it was necessary to recruit CBP to activate enhancers for epidermal differentiation gene expression [4]. In gastric cancer, overexpressed Klf3 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while suppressed Klf3 inhibited these behaviors, and Klf3 could directly bind to the WNT1 promoter to regulate its expression and activate the WNT/β-catenin signaling pathway [5]. Decreased Klf3 expression via miR-660-5p targeting suppressed gastric cancer cell progression [6]. In colon cancer, miR-92b-3p augmented cancer development through inhibiting Klf3 [7]. In lung cancer, KLF3 silencing promoted epithelial-mesenchymal transition (EMT) and metastasis, and its role was dependent on the STAT3 signaling pathway [8].

In conclusion, Klf3 plays essential roles in adipogenesis, glucose metabolism, cell differentiation, and cancer development. Studies using KO/CKO mouse models or other loss-of-function experiments have revealed its functions in these biological processes and disease conditions, providing insights into potential therapeutic targets for obesity, diabetes, and various cancers.