Klf12, also known as Krüppel-like factor 12, is a transcriptional regulator. It functions as a transcriptional repressor and is involved in multiple biological processes, such as angiogenesis, neural tube development, and NK cell proliferation. It is associated with pathways like those related to cancer metastasis, immunotherapy response, and cell cycle regulation, highlighting its overall biological importance. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, have been crucial for studying Klf12's functions [1,3].

In cancer research, Klf12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC) by regulating L1CAM expression [1]. In non-small cell lung cancer, Klf12 transcriptionally regulates PD-L1 expression, and its knockout in immunocompetent mice inhibits tumor growth and promotes CD8+ T cell infiltration [2]. In breast cancer, Klf12 promotes cell proliferation by reducing p21 transcription in p53-dependent and p53-independent manners [4]. In NK cell studies, Klf12-deficient NK cells from bone marrow chimeric mice show impaired proliferation, altered IFN-γ production, and degranulation in response to mouse CMV infection [3]. In cardiac remodeling, overexpression of Klf12 in cardiac fibroblasts of male mice exacerbates angiotensin II-induced cardiac remodeling by inhibiting SMAD7 [5]. In airway epithelial cells, Klf12 suppresses lipopolysaccharide-induced inflammatory response, oxidative stress, pyroptosis, and ER stress via the NF-κB pathway [6].

In conclusion, Klf12 is a key transcriptional regulator involved in diverse biological processes. Studies using KO/CKO mouse models have revealed its significant roles in cancer (including metastasis, drug resistance, and immunotherapy response), NK cell function, cardiac remodeling, and airway epithelial cell responses to inflammation. Understanding Klf12's functions provides potential therapeutic targets for related diseases.

References:

1. Zhang, Hao, Zheng, Yujia, Wang, Zhen, Li, Chunxiang, He, Jie. 2024. KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression. In Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 76, 101096. doi:10.1016/j.drup.2024.101096. https://pubmed.ncbi.nlm.nih.gov/38924996/

2. Pan, Xiaohui, Zhang, Wenxin, Wang, Longsheng, Ding, Ling, Yang, Bo. 2023. KLF12 transcriptionally regulates PD-L1 expression in non-small cell lung cancer. In Molecular oncology, 17, 2659-2674. doi:10.1002/1878-0261.13512. https://pubmed.ncbi.nlm.nih.gov/37606530/

3. Lam, Viola C, Folkersen, Lasse, Aguilar, Oscar A, Lanier, Lewis L. 2019. KLF12 Regulates Mouse NK Cell Proliferation. In Journal of immunology (Baltimore, Md. : 1950), 203, 981-989. doi:10.4049/jimmunol.1900396. https://pubmed.ncbi.nlm.nih.gov/31300511/

4. Li, Yanan, Li, Shujing, Shi, Xiaoxia, Ren, Ping, Wu, Huijian. 2023. KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner. In Cell death & disease, 14, 313. doi:10.1038/s41419-023-05824-x. https://pubmed.ncbi.nlm.nih.gov/37156774/

5. Hu, Min, Huang, Shi-Yu, Gao, Yi-Peng, Zeng, Xiao-Feng, Tang, Qi-Zhu. 2025. KLF12 Aggravates Angiotensin II-Induced Cardiac Remodeling in Male Mice by Transcriptionally Inhibiting SMAD7. In Journal of the American Heart Association, 14, e037455. doi:10.1161/JAHA.124.037455. https://pubmed.ncbi.nlm.nih.gov/39895521/

6. Xu, Xiujuan, Yu, Yiping. 2025. KLF12 inhibits lipopolysaccharide-induced inflammatory responses, oxidative stress, pyroptosis, and endoplasmic reticulum stress in human airway epithelial cells through inhibition of the NF-κB pathway. In Biochimica et biophysica acta. Molecular cell research, 1872, 119917. doi:10.1016/j.bbamcr.2025.119917. https://pubmed.ncbi.nlm.nih.gov/39938687/