PSMD2, encoding 26S proteasome non-ATPase regulatory subunit 2, is a key component of the ubiquitin-proteasome system, which is crucial for regulating intracellular protein levels. This system collaborates with the autophagy-lysosomal system in maintaining protein homeostasis, a process often dysregulated in malignancy [1].

PSMD2 has been shown to act as an oncogene in multiple cancers. In esophageal squamous cell carcinoma (ESCC), its overexpression promotes cell growth by inhibiting autophagy via activating the mTOR pathway through upregulating ASS1, correlating with tumor progression and poor prognosis [1]. In bladder cancer, elevated PSMD2 expression promotes cancer progression and is associated with immune infiltration, influencing the cell cycle, antigen processing, and multiple signaling pathways [2]. In renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors, PSMD2 overexpression is linked to resistance, decreased progression-free survival, and impaired function of tumor-infiltrating lymphocytes [3]. In lung adenocarcinoma, high PSMD2 expression is correlated with poor prognosis and immune cell infiltration levels [4]. In nasopharyngeal carcinoma, DNAJA4 suppresses metastasis via PSMD2-mediated MYH9 degradation [5]. In breast cancer, RACK1 promotes cancer progression by competitively inhibiting β-catenin's binding to PSMD2, enhancing β-catenin stability [6]. Also in breast cancer, PSMD2 regulates cell proliferation and cell cycle progression by modulating p21 and p27 proteasomal degradation [7]. In HepG2 cells, PSMD2 promotes proliferation by facilitating cellular lipid droplet accumulation [8].

In conclusion, PSMD2 plays significant roles in cancer development and progression across multiple cancer types, mainly through its impact on autophagy, cell cycle regulation, immune infiltration, and protein degradation. Understanding PSMD2's functions through various in vivo and in vitro models provides valuable insights into cancer mechanisms, potentially guiding the development of novel cancer therapies targeting this gene.

References:

1. Liu, Yachen, Wu, Meng, Xu, Shuxiang, Xu, Yang, Yu, Lili. 2023. PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy. In Cell & bioscience, 13, 67. doi:10.1186/s13578-023-01016-4. https://pubmed.ncbi.nlm.nih.gov/36998052/

2. Wang, Song, Wang, He, Zhu, Shaoxing, Wang, Zongping. 2022. PSMD2 promotes the progression of bladder cancer and is correlated with immune infiltration. In Frontiers in oncology, 12, 1058506. doi:10.3389/fonc.2022.1058506. https://pubmed.ncbi.nlm.nih.gov/36505799/

3. Xu, Xianglai, Wang, Jiahao, Wang, Ying, Wang, Jiajun, Guo, Jianming. 2024. PSMD2 overexpression as a biomarker for resistance and prognosis in renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors. In Cellular oncology (Dordrecht, Netherlands), 47, 1943-1956. doi:10.1007/s13402-024-00977-z. https://pubmed.ncbi.nlm.nih.gov/39222176/

4. Zhao, Huihui, Lu, Guojun. 2022. Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma. In Frontiers in genetics, 13, 905581. doi:10.3389/fgene.2022.905581. https://pubmed.ncbi.nlm.nih.gov/35754829/

5. Zhang, Qun, Feng, Ping, Zhu, Xun-Hua, He, Shi-Wei, Li, Ying-Qing. 2023. DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation. In Cell death & disease, 14, 697. doi:10.1038/s41419-023-06225-w. https://pubmed.ncbi.nlm.nih.gov/37875476/

6. Tian, Ruinan, Tian, Jianfei, Zuo, Xiaoyan, Niu, Ruifang, Zhang, Fei. 2023. RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin. In Cell death & disease, 14, 685. doi:10.1038/s41419-023-06191-3. https://pubmed.ncbi.nlm.nih.gov/37848434/

7. Li, Yunhai, Huang, Jing, Zeng, Beilei, Li, Hongzhong, Ren, Guosheng. 2018. PSMD2 regulates breast cancer cell proliferation and cell cycle progression by modulating p21 and p27 proteasomal degradation. In Cancer letters, 430, 109-122. doi:10.1016/j.canlet.2018.05.018. https://pubmed.ncbi.nlm.nih.gov/29777785/

8. Tan, Yanjie, Jin, Yi, Wu, Xiang, Ren, Zhuqing. 2019. PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism. In BMC molecular biology, 20, 24. doi:10.1186/s12867-019-0141-z. https://pubmed.ncbi.nlm.nih.gov/31703613/