Klf16, a member of the Kruppel-like factor (KLF) family, is a transcription factor [8]. It is involved in multiple biological functions, such as regulating lipid metabolism, being associated with adipose tissue development and glucose metabolism [8]. It also plays roles in various signaling pathways, like those related to cancer, immunity, and oxidative stress [8]. Genetic models, especially KO/CKO mouse models, are valuable for studying Klf16's functions.

In the context of non-alcoholic fatty liver disease (NAFLD), Klf16 expression was decreased in patients, mouse models, and oleic acid and palmitic acid-cochallenged hepatocytes [1]. Hepatic Klf16 knockout in mice fed a high-fat diet impaired fatty acid oxidation, aggravated mitochondrial stress, ROS burden, and advanced hepatic steatosis and insulin resistance [1]. Conversely, Klf16 overexpression reduced lipid deposition and improved insulin resistance by directly binding to the promoter of peroxisome proliferator-activated receptor α (PPARα), accelerating fatty acid oxidation, and attenuating mitochondrial and oxidative stress [1].

In summary, Klf16 is crucial in regulating hepatic lipid homeostasis and redox balance. Its deficiency in KO mouse models has revealed its role in promoting insulin resistance and hepatic steatosis in the context of NAFLD. Klf16 also has implications in cancer development as studies in pancreatic adenocarcinoma, bladder cancer, prostate cancer, colorectal carcinoma, and retinoblastoma have shown its involvement in promoting cell proliferation, migration, and tumor growth through various molecular mechanisms [2,3,4,5,6,7].

References:

1. Sun, Nannan, Shen, Chuangpeng, Zhang, Lei, Chang, Yongsheng, Gao, Yong. 2020. Hepatic Krüppel-like factor 16 (KLF16) targets PPARα to improve steatohepatitis and insulin resistance. In Gut, 70, 2183-2195. doi:10.1136/gutjnl-2020-321774. https://pubmed.ncbi.nlm.nih.gov/33257471/

2. Mi, Wei, Zheng, Zhi, Lu, Jiong-Di, Zhang, Jun, Li, Fei. . KLF16 promotes pancreatic adenocarcinoma cell proliferation and migration by positively regulating SMAD6. In World journal of gastrointestinal oncology, 14, 2157-2169. doi:10.4251/wjgo.v14.i11.2157. https://pubmed.ncbi.nlm.nih.gov/36438710/

3. Zheng, Lisi, Wang, Jingxuan, Han, Shan, Wu, Yuanzhong, Kang, Tiebang. 2024. The KLF16/MYC feedback loop is a therapeutic target in bladder cancer. In Journal of experimental & clinical cancer research : CR, 43, 303. doi:10.1186/s13046-024-03224-3. https://pubmed.ncbi.nlm.nih.gov/39551759/

4. Ma, Xiao-Dan, Xu, Shui-Dan, Hao, Shi-Hui, Xie, Dan, Wang, Feng-Wei. 2022. KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming. In Molecular therapy : the journal of the American Society of Gene Therapy, 30, 2828-2843. doi:10.1016/j.ymthe.2022.04.022. https://pubmed.ncbi.nlm.nih.gov/35524408/

5. Chen, Xiaosong, Wang, Ping, Ou, Tongwen, Li, Jin. 2022. KLF16 Downregulates the Expression of Tumor Suppressor Gene TGFBR3 to Promote Bladder Cancer Proliferation and Migration. In Cancer management and research, 14, 465-477. doi:10.2147/CMAR.S334521. https://pubmed.ncbi.nlm.nih.gov/35173481/

6. Zhang, Jun, Yu, Wandong, Wang, Xilong, Wu, Denglong, Shi, Guowei. 2020. KLF16 Affects the MYC Signature and Tumor Growth in Prostate Cancer. In OncoTargets and therapy, 13, 1303-1310. doi:10.2147/OTT.S233495. https://pubmed.ncbi.nlm.nih.gov/32103997/

7. Zhang, Jing-Xue, Yan, Xue-Jing, Wu, Shen, Liu, Qian, Ma, Jian-Min. 2020. KLF16 overexpression deleteriously affects the proliferation and migration of retinoblastoma by transcriptionally repressing BCL2L15. In Biochemical and biophysical research communications, 529, 977-983. doi:10.1016/j.bbrc.2020.06.027. https://pubmed.ncbi.nlm.nih.gov/32819608/

8. Yuce, Kemal, Ozkan, Ahmet Ismail. 2023. The kruppel-like factor (KLF) family, diseases, and physiological events. In Gene, 895, 148027. doi:10.1016/j.gene.2023.148027. https://pubmed.ncbi.nlm.nih.gov/38000704/