Panoply™ Human HDAC4 Over-expressing Stable Cell Line

Histone deacetylases (HDACs) are involved in tumor progression, and some have been successfully used as targets for cancer treatment. Previous microarray screening revealed elevated expression levels of class IIa histone deacetylase 4 (HDAC4). However, the role and mechanisms of HDAC4 dysregulation in nasopharyngeal carcinoma (NPC) tumor growth and metastasis remain unclear. Here, researchers first confirmed that HDAC4 expression levels were significantly higher in primary and metastatic NPC tissues compared to normal nasopharyngeal epithelial tissues, and found that high HDAC4 expression predicted poorer overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated the G1/S phase transition of the cell cycle and induced epithelial-mesenchymal transition, thereby promoting the proliferation, migration, and invasion of NPC cells in vitro, as well as tumor growth and lung metastasis in vivo. Interestingly, knockdown of N-CoR eliminated the effects of HDAC4 on the invasive and migratory capabilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter, inhibiting E-cadherin transcription. The researchers also found that the HDAC4 inhibitor tasquinimod could inhibit NPC tumor growth. Therefore, HDAC4 may serve as a potential diagnostic marker and therapeutic target for NPC patients.

Based on the endogenous expression of HDAC4 in NPC cell lines, researchers constructed stable HDAC4-overexpressing S26 and 6-10B cell lines, which have low basal HDAC4 expression levels (Figure 1A). CCK8 and colony formation assays showed that cell proliferation and colony formation ability were significantly enhanced in HDAC4-overexpressing cells compared to control cells (Figure 1B, C). Furthermore, Transwell assays showed that HDAC4-overexpressing cells exhibited significantly enhanced in vitro invasion and migration abilities compared to control cells (Figure 1D, E). These results indicate that the proliferation, migration, and invasion of NPC cells are regulated by HDAC4, and this regulatory effect depends on the expression level of HDAC4. To evaluate the effect of HDAC4 on NPC growth and metastasis in vivo, researchers established a subcutaneous xenograft model by subcutaneously injecting control or HDAC4-overexpressing 6-10B cells into nude mice. Tumor weight results showed that subcutaneous tumor growth was significantly increased in the HDAC4-overexpressing cell group compared to the control group (Figure 1F). In addition, lung metastasis was significantly increased in the HDAC4-overexpressing 6-10B cell group compared to the control group (Figure 1G). In summary, these results suggest that ectopic expression of HDAC4 may promote the growth and metastasis of NPC.

Figure 1. Overexpression of HDAC4 promotes tumor growth and metastasis in NPC. (Cheng C, et al., 2021)