HDAC2, short for histone deacetylase 2, is a crucial enzyme in the nucleus that deacetylates histones H3 and H4. It plays a vital role in modifying chromatin structures and functions as a transcriptional regulator to control the expression of various genes. HDAC2 is involved in multiple biological pathways and has overall significance in maintaining normal cellular functions and is relevant in disease contexts [1].

In colorectal cancer (CRC), HDAC2 deletion or knockdown induced epithelial-mesenchymal transition (EMT) and metastasis by upregulating the long non-coding RNA H19, indicating its role as a CRC metastasis suppressor [2]. In clear cell renal cell carcinoma (ccRCC), HDAC2 inhibitors resensitize ccRCC to tyrosine kinase inhibitors through the YY1/HDAC2 complex [3]. Inhibiting HDAC2 in CRC xenograft-bearing animals activates NLRP3/GSDMD-mediated pyroptosis and enhances the therapeutic effect, suggesting HDAC2 as a potential therapeutic target for antitumor therapy in CRC [4]. In hepatocellular carcinoma (HCC), HDAC2 promotes autophagy-associated malignant progression by transcriptionally activating LAPTM4B, and its selective inhibitor alleviates HCC malignant development [5]. In pancreatic ductal adenocarcinoma (PDAC), HDAC2 controls cell cycle in vitro and metastasis in vivo, especially in undifferentiated, mesenchymal PDAC cells [6].

In conclusion, HDAC2 has diverse functions in different diseases, regulating processes such as metastasis, autophagy, and drug sensitivity. Gene knockout or knockdown models in these cancer types have been instrumental in revealing these functions, highlighting the importance of HDAC2 as a potential therapeutic target in oncology research.