Panoply™ Human HDAC2 Knockdown Stable Cell Line

Hepatocellular carcinoma (HCC) is a significant global health challenge. Autophagy activation plays a crucial role in promoting cancer cell proliferation and survival. However, the upstream regulatory networks and mechanisms that regulate autophagy in HCC remain unclear. This study demonstrates that histone deacetylase 2 (HDAC2) regulates autophagy in HCC. HDAC2 expression is elevated in HCC tissues, and high HDAC2 expression is closely associated with poor prognosis in HCC patients. Comprehensive in vitro and in vivo studies confirmed that HDAC2 promotes autophagy and autophagy-related malignant progression in HCC. Mechanistic studies revealed that HDAC2 specifically binds to four different binding sites on the lysosome-associated protein transmembrane 4-β (LAPTM4B) promoter, enhancing its transcriptional activation and thus driving autophagy-related malignant progression in HCC. These findings establish LAPTM4B as a direct target gene of HDAC2. Furthermore, selective inhibitors of HDAC2 effectively alleviate the malignant progression of HCC. Multivariate Cox regression analysis of 105 human HCC samples showed that HDAC2 expression is an independent predictor of HCC prognosis. This study highlights the critical role of the HDAC2-LAPTM4B axis in regulating autophagy during HCC malignant progression and underscores the potential of targeting HDAC2 in preventing and inhibiting HCC malignant progression.

Given that HDAC2 is crucial for promoting autophagy in hepatocellular carcinoma (HCC) and that autophagy is associated with cancer malignancy, researchers investigated the pro-tumor function of HDAC2 and its link to autophagy. Colony formation assays and CCK-8 (Cell Counting Kit-8) assays showed that HDAC2 knockdown led to decreased cell proliferation and colony-forming ability compared to the control group. In HDAC2-knockdown HepG2 and Huh7 cells, cell doubling time increased by 38.4 hours and 7.2 hours, respectively, and the number of colonies decreased by 40% and 60%, respectively (Figure 1A, B). Conversely, HDAC2-overexpressing cells exhibited stronger proliferation and colony-forming ability than the control group. The doubling time of HDAC2-overexpressing HCC-LM3 and SNU-449 cells was shortened by 45.6 hours and 31.2 hours, respectively, and the number of colonies was 1.8 times and 1.9 times that of the control group, respectively (Figure 1C, D). Furthermore, flow cytometry results showed a higher apoptosis rate in HDAC2-knockdown cells, while HDAC2-overexpressing cells showed the opposite result (Figure 1E, F).

Figure 1. HDAC2 promotes autophagy-associated HCC malignancy. (Wang M, et al., 2024)