Suppressed ZNF816 expression enhance keratinocyte growth and reduce apoptosis by activating the AKT signaling pathway

Abstract

Abstract Background Psoriasis, a chronic inflammatory skin disorder defined by keratinocytes hyperproliferation and inflammatory cell permeation, has shown susceptibility links to ZNF816 in our genome-wide association study (GWAS) data. Nonetheless, the precise role of ZNF816 in psoriasis progression remains elusive. This study aimed to explore its impact on epidermal keratinocyte proliferation and apoptosis. Methods We utilized immunohistochemistry and Western blotting to assess ZNF816 expression in psoriasis lesions and surrounding normal skin tissue. HaCaT cells were transfected with an ectopic ZNF816 plasmid. Cell proliferation, cell cycle progression, apoptosis, and migratory capacity were measured using MTS assays, flow cytometry, and wound healing assays, respectively. The mitochondrial membrane potential (MMP) and Reactive Oxygen Species (ROS) were employed to gauge the mitochondrial function and cellular oxidative release. Western blotting was used to evaluate the expression of ZNF816, caspase-3, Bax, Bcl-2, and the AKT pathway following ZNF816 overexpression or knockdown in HaCaT cells. Results Notably, psoriasis patient skin lesions exhibited decreased ZNF816 levels compared to nonlesional tissue. ZNF816 knockdown enhanced cell viability and promoted keratinocyte proliferation, as evidenced by MTS and wound healing assays. Reduced ZNF816 induced G2/M phase arrest and altered the expression of cell cycle and apoptosis regulatory proteins. Additionally, ZNF816 knockdown activated the AKT signaling pathway. Conclusion Reduced ZNF816 expression appears to contribute to keratinocyte hyperproliferation, potentially playing a role in the initiation and progression of psoriasis. ZNF816 knockdown promoted HaCaT cell growth while inhibiting apoptosis through activation of the AKT pathway.