{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T20:31:09Z","timestamp":1787085069558,"version":"build-2736575974"},"reference-count":30,"publisher":"Begell House","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crit Rev Immunol"],"published-print":{"date-parts":[[2026]]},"abstract":"<p>Gallbladder cancer (GBC) is a prevalent and aggressive malignancy of the biliary system. Studies have revealed that Proteasome 26S subunit ATPase 2 (PSMC2) is overexpressed and associated with the development process of several cancers. However, the specific role in GBC remains unknown. This study aims to explore the association between PSMC2 and GBC pathogenesis. We assessed PSMC2 expression from normal and GBC patient samples. Using Cell Counting Kit-8 (CCK-8), colony formation, scratch, and Transwell migration assays, we investigated the effects of PSMC2 on the proliferation and migration of GBC cells. Subsequently, through bioinformatics analysis, we identified the cell cycle pathways related to PSMC2 in GBC cells. Using flow cytometry, we identified that knocking down PSMC2 could alter the cell cycle in GBC cells. Then, through bioinformatics analysis and Western blot assay, we discovered the relationship between the AKT\/Cyclin D1\/CDK6 pathway and the cell cycle and used an RAC-alpha serine\/threonine-protein kinase (AKT) inhibitor and an Cyclin-Dependent Kinase 6 (CDK6) inhibitor to restore the GBC cell proliferation induced by PSMC2 overexpression in order to detect the mechanism of PSMC2's role in GBC. We found that PSMC2 was observably upregulated in GBC patient samples. &lt;i&gt;In vitro&lt;\/i&gt; experiments demonstrated that knocking down PSMC2 significantly suppressed the GBC cells' proliferation and migration abilities. Bioinformatics assays showed a significant enrichment of the cell cycle pathway in both the GO and KEGG databases. Furthermore, cell cycle-related genes CDK6 and Cyclin D1 were significantly upregulated in PSMC2-high expressed clusters. Then we identified that knockdown of PSMC2 could suppress AKT activation and reduce the expression of Cyclin D1 and CDK6. Moreover, treatment with the AKT inhibitor could restore the upregulated CDK6 expression after PSMC2 overexpression, and treatment with the CDK6 inhibitor restored the progression and altered the cell cycle distribution in GBC cells induced by PSMC2 overexpression. PSMC2 was significantly upregulated in GBC tissues and cell lines. PSMC2 expression promotes progression and migration in GBC cells, potentially through regulation of the AKT\/Cyclin D1\/CDK6 signaling pathway.<\/p>","DOI":"10.1615\/critrevimmunol.2026063698","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:13:06Z","timestamp":1779469986000},"page":"45-56","source":"Crossref","is-referenced-by-count":0,"title":["PSMC2 Promotes Gallbladder Carcinoma Progression by Regulating the AKT\/Cyclin D1\/CDK6 Signaling Axis"],"prefix":"10.1615","volume":"46","author":[{"given":"Yiming","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"Roa JC, Garc\u00eda P, Kapoor VK, Maithel SK, Javle M, Koshiol J. 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