Psme3, also known as proteasome activator subunit 3 or REGγ or PA28, is a subunit of the proteasome activator complex. It is involved in protein degradation and has been associated with multiple biological functions, including immune responses, cell cycle regulation, and stem cell regulation [3]. It participates in various pathways such as the TGF-β/SMAD signaling pathway [2].

In cancer, Psme3 has been shown to play significant roles. In cervical cancer, its knockdown enhanced radiosensitivity and suppressed abnormal glycolysis, as it increased the expression of PARP1 via c-myc [1]. In lung adenocarcinoma, downregulation of Psme3 inhibited cell proliferation, invasion, and migration, and caused cell cycle arrest at the G1/S phase, with the TGF-β/SMAD pathway being closely related [2]. In colorectal cancer, silencing Psme3 inhibited cell proliferation, invasion, and migration, and enhanced radiosensitivity by triggering cell cycle arrest at the G2/M phase through down-regulating cyclinB1 and CDK1 [4]. In pancreatic cancer, Psme3 promoted TGFB1 secretion to induce pancreatic stellate cell proliferation [5]. In breast cancer, overexpression of Psme3 induced epithelial-mesenchymal transition, increased expression of cancer stem cell markers, and influenced the tumor immune microenvironment [7]. In preeclampsia, downregulated Psme3 in the placenta promoted trophoblast cell apoptosis by repressing UBE2V2 degradation [6].

In conclusion, Psme3 is crucial in multiple biological processes and disease conditions, especially in various cancers and preeclampsia. Studies using loss-of-function approaches in these contexts have revealed its significant role in promoting cancer cell progression and in the pathogenesis of preeclampsia, highlighting its potential as a therapeutic target.