Programmed cell death 4 (PDCD4), mapped at chromosome 10q24, encodes a 469-amino-acid protein. It is a tumor suppressor gene, playing crucial roles in processes like cell apoptosis, transformation, invasion, and tumor progression. PDCD4 inhibits protein translation by binding to eIF4A via its MA-3 domains or directly to 5' mRNA internal ribosome entry sites with an RNA-binding domain, thus suppressing tumor development [1]. It is also involved in various signaling pathways, and its expression is regulated by numerous factors such as non-coding RNAs, proteasomes, estrogen, natural compounds, and inflammation [1].

In NASH, PDCD4-deficient mice showed spontaneous NASH progression as PDCD4-deficient hepatocytes had elevated MHCII expression due to CIITA activation, resembling antigen-presenting cells and directly activating CD4+ T cells to release inflammatory factors. This indicates PDCD4's protective role in NASH by regulating CIITA and MHCII expression [2]. In premature ovarian insufficiency (POI), PDCD4 expression was increased in POI-induced mice and patients. PDCD4 knockout in mice with POI significantly increased anti-Müllerian hormone, estradiol, and developing follicles, involving the PI3K-AKT-Bcl2/Bax signaling pathway [3]. In atrial fibrillation, overexpression of PDCD4 in mouse atrial myocytes increased fibrotic and pro-inflammatory factors, while its silencing had the opposite effect, suggesting PDCD4 promotes inflammation and fibrosis by activating the PPAR-γ/NF-κB pathway [4].

In conclusion, PDCD4 is a significant tumor suppressor gene with multiple functions in various biological processes and disease conditions. Gene knockout mouse models have revealed its roles in NASH, POI, and atrial fibrillation, helping us understand its functions in disease development and potentially providing new therapeutic targets for these diseases.