HDAC11, histone deacetylase 11, is a unique member of the histone deacetylase family. It plays a crucial role in regulating gene expression and protein function through its deacetylase activity, which is involved in various epigenetic mechanisms. HDAC11 participates in diverse biological processes and is associated with multiple pathways, making it of great biological importance. Genetic models, such as knockout mouse models, have been instrumental in studying its functions [1,2,3,4,5,6,7,8,9,10].

In a conditional knockout mouse model, depletion of HDAC11 reduced hepatocellular tumorigenesis and prolonged survival. Loss of HDAC11 increased LKB1 transcription, activated the AMPK signaling pathway, inhibited the glycolysis pathway, and suppressed cancer stemness and HCC progression. Also, HDAC11 overexpression reduced HCC sensitivity to sorafenib, suggesting it as a new target for kinase-resistant HCC combination therapy [3]. In another study, adipocyte-specific deletion of HDAC11 in mice robustly induced UCP1 in adipose tissue, increasing body temperature, highlighting its role as a suppressor of thermogenesis [7].

In conclusion, HDAC11 is involved in a wide range of biological functions, including tumor growth regulation, metabolic processes, and immune regulation. Studies using KO/CKO mouse models have revealed its significance in diseases such as cancer and metabolic disorders, providing potential therapeutic targets for these conditions [3,7].

References:

1. Liu, Yan, Tong, Xuechao, Hu, Weina, Chen, Da. 2023. HDAC11: A novel target for improved cancer therapy. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 166, 115418. doi:10.1016/j.biopha.2023.115418. https://pubmed.ncbi.nlm.nih.gov/37659201/

2. Chen, Huizhen, Xie, Chunguang, Chen, Qiu, Zhuang, Shougang. 2022. HDAC11, an emerging therapeutic target for metabolic disorders. In Frontiers in endocrinology, 13, 989305. doi:10.3389/fendo.2022.989305. https://pubmed.ncbi.nlm.nih.gov/36339432/

3. Bi, Lei, Ren, Yidan, Feng, Maoxiao, Tang, Bo, Wang, Yunshan. 2021. HDAC11 Regulates Glycolysis through the LKB1/AMPK Signaling Pathway to Maintain Hepatocellular Carcinoma Stemness. In Cancer research, 81, 2015-2028. doi:10.1158/0008-5472.CAN-20-3044. https://pubmed.ncbi.nlm.nih.gov/33602787/

4. Yao, Feng, Jin, Zhen, Zheng, Zihan, Gu, Jianli, Lin, Rong. 2022. HDAC11 promotes both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells. In Cell death discovery, 8, 112. doi:10.1038/s41420-022-00906-9. https://pubmed.ncbi.nlm.nih.gov/35279683/

5. Liu, Shan-Shan, Wu, Fei, Jin, Yue-Mei, Chang, Wei-Qin, Xu, Tian-Min. 2020. HDAC11: a rising star in epigenetics. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 131, 110607. doi:10.1016/j.biopha.2020.110607. https://pubmed.ncbi.nlm.nih.gov/32841898/

6. Núñez-Álvarez, Yaiza, Suelves, Mònica. 2021. HDAC11: a multifaceted histone deacetylase with proficient fatty deacylase activity and its roles in physiological processes. In The FEBS journal, 289, 2771-2792. doi:10.1111/febs.15895. https://pubmed.ncbi.nlm.nih.gov/33891374/

7. Robinson, Emma L, Bagchi, Rushita A, Major, Jennifer L, Matsuda, Jennifer L, McKinsey, Timothy A. 2023. HDAC11 inhibition triggers bimodal thermogenic pathways to circumvent adipocyte catecholamine resistance. In The Journal of clinical investigation, 133, . doi:10.1172/JCI168192. https://pubmed.ncbi.nlm.nih.gov/37607030/

8. Yanginlar, Cansu, Logie, Colin. 2017. HDAC11 is a regulator of diverse immune functions. In Biochimica et biophysica acta. Gene regulatory mechanisms, 1861, 54-59. doi:10.1016/j.bbagrm.2017.12.002. https://pubmed.ncbi.nlm.nih.gov/29222071/

9. Yang, Hong, Chen, Lingling, Sun, Qian, Muhammad, Saeed, Sun, Chao. 2021. The role of HDAC11 in obesity-related metabolic disorders: A critical review. In Journal of cellular physiology, 236, 5582-5591. doi:10.1002/jcp.30286. https://pubmed.ncbi.nlm.nih.gov/33481312/

10. He, Yan, Zheng, Can-Can, Yang, Jing, Liu, Jin-Bao, Li, Bin. 2023. Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance. In Cell discovery, 9, 74. doi:10.1038/s41421-023-00570-y. https://pubmed.ncbi.nlm.nih.gov/37460462/