HDAC11, histone deacetylase 11, is the sole member of the class IV HDAC subfamily. It plays a vital role in regulating gene expression and protein function by deacetylating histone and non-histone proteins. HDAC11 is involved in diverse biological pathways such as DNA replication, immune regulation, and metabolic processes [1,3,4]. Its abnormal expression is associated with various diseases, making it an attractive therapeutic target. Genetic models, like knockout mice, have been crucial in studying its functions.

In a conditional knockout mouse model of hepatocellular carcinoma (HCC), depletion of HDAC11 reduced hepatocellular tumorigenesis and prolonged survival. It was found that HDAC11 suppresses LKB1 expression in HCC, and loss of HDAC11 increased LKB1 transcription, activating the AMPK signaling pathway and inhibiting glycolysis, thus suppressing cancer stemness and HCC progression. Also, HDAC11 overexpression reduced HCC sensitivity to sorafenib, suggesting its potential as a target for kinase-resistant HCC treatment [2]. In another study, adipocyte-specific deletion of HDAC11 in mice led to increased body temperature due to robust induction of UCP1 in adipose tissue, indicating HDAC11's role as a suppressor of thermogenesis [5].

In conclusion, HDAC11 is a key regulator in multiple biological processes. Model-based research, especially through KO/CKO mouse models, has revealed its significant roles in cancer, metabolic disorders, and immune-related diseases. These findings highlight HDAC11 as a potential therapeutic target for treating conditions such as HCC, obesity-related metabolic disorders, and certain immune-mediated diseases [1,2,5].

References:

1. 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/

2. 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/

3. 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/

4. 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/

5. 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/