Psme3, also known as proteasome activator complex subunit 3 or REGγ or PA28, is a subunit of the 11S proteasome regulator complex. It is involved in protein degradation, immune responses, stem cell regulation, and is associated with multiple signaling pathways such as TGF-β/SMAD [1,3]. It plays a crucial role in various biological processes and is of great significance in understanding disease mechanisms [1,3].

Functional studies have shown that Psme3 has diverse effects in different diseases. In cervical cancer, depletion of Psme3 enhanced radiosensitivity and suppressed abnormal glycolysis [2]. In lung adenocarcinoma, down-regulation of Psme3 inhibited cell proliferation, invasion, and migration, and caused cell cycle arrest at the G1/S phase [3]. In colorectal cancer, silencing Psme3 inhibited cell proliferation, invasion, and migration, and enhanced radiosensitivity by triggering cell cycle arrest at the G2/M phase [4]. In breast cancer, overexpression of Psme3 induced epithelial-mesenchymal transition, increased the expression of cancer stem cell markers, and influenced the tumor immune microenvironment [7]. In pancreatic cancer, Psme3 promoted TGFB1 secretion by pancreatic cancer cells to induce pancreatic stellate cell proliferation [5]. In severe preeclampsia, down-regulated Psme3 in placentas promoted trophoblast cell apoptosis [6].

In conclusion, Psme3 is involved in multiple biological functions including cell cycle regulation, apoptosis, and immune response modulation. Through loss-of-function experiments in various cancer types and in preeclampsia, its role in disease progression has been revealed. These findings provide potential therapeutic targets for cancers and insights into the pathogenesis of preeclampsia.

References:

1. Dong, Chengyuan, Guo, Yadong, Yang, Yanrong, Ge, Xin. 2024. Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation. In Frontiers in immunology, 15, 1295693. doi:10.3389/fimmu.2024.1295693. https://pubmed.ncbi.nlm.nih.gov/38312840/

2. Wei, Xing, Sun, Ke, Li, Shubo, Lin, Cheng, Wei, Zhongheng. 2023. PSME3 induces radioresistance and enhances aerobic glycolysis in cervical cancer by regulating PARP1. In Tissue & cell, 83, 102151. doi:10.1016/j.tice.2023.102151. https://pubmed.ncbi.nlm.nih.gov/37467687/

3. Wang, Shuai, Li, Yongmeng, Jin, Kai, Zhang, Huiying, Tian, Hui. 2024. PSME3 promotes lung adenocarcinoma development by regulating the TGF-β/SMAD signaling pathway. In Translational lung cancer research, 13, 1331-1345. doi:10.21037/tlcr-24-340. https://pubmed.ncbi.nlm.nih.gov/38973962/

4. Song, Wen, Guo, Cuiping, Chen, Jianxiong, Geng, Jian, Zhou, Jun. 2019. Silencing PSME3 induces colorectal cancer radiosensitivity by downregulating the expression of cyclin B1 and CKD1. In Experimental biology and medicine (Maywood, N.J.), 244, 1409-1418. doi:10.1177/1535370219883408. https://pubmed.ncbi.nlm.nih.gov/31630568/

5. Yu, Lianyuan, Li, Jun-Jie, Liang, Xiao-Long, Wu, Huanwen, Liang, Zhiyong. 2019. PSME3 Promotes TGFB1 Secretion by Pancreatic Cancer Cells to Induce Pancreatic Stellate Cell Proliferation. In Journal of Cancer, 10, 2128-2138. doi:10.7150/jca.30235. https://pubmed.ncbi.nlm.nih.gov/31205573/

6. Liu, Lin, Chen, Hui, Wu, Renfei, Li, Lei, Ge, Xiaoli. 2025. Downregulated PSME3 Contributes to Severe Preeclampsia by Promoting Trophoblast Cell Apoptosis. In Hypertension (Dallas, Tex. : 1979), 82, 690-703. doi:10.1161/HYPERTENSIONAHA.124.22718. https://pubmed.ncbi.nlm.nih.gov/39906994/

7. Yi, Ziying, Yang, Dejuan, Liao, Xuelian, Wang, Yongsheng, Wang, Xiaoyi. 2017. PSME3 induces epithelial-mesenchymal transition with inducing the expression of CSC markers and immunosuppression in breast cancer. In Experimental cell research, 358, 87-93. doi:10.1016/j.yexcr.2017.05.017. https://pubmed.ncbi.nlm.nih.gov/28529105/