Academic Journal
KPNA2 knockdown suppresses gastric cancer progression through modulation of the β-catenin/EMT signaling axis, inducing cell cycle arrest, apoptosis, and reduced metastatic capacity.
| Τίτλος: | KPNA2 knockdown suppresses gastric cancer progression through modulation of the β-catenin/EMT signaling axis, inducing cell cycle arrest, apoptosis, and reduced metastatic capacity. |
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| Συγγραφείς: | Zhu H; Department of Gastrointestinal Surgery, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, No. 666, Shengli Road, Nantong, 226001, Jiangsu, China., Niu T; Department of Gastrointestinal Surgery, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, No. 666, Shengli Road, Nantong, 226001, Jiangsu, China., Feng S; Department of Gastrointestinal Surgery, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, No. 666, Shengli Road, Nantong, 226001, Jiangsu, China., Shi C; Department of Pathology, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, Nantong, 226001, Jiangsu, China., Tang C; Department of Gastrointestinal Surgery, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, No. 666, Shengli Road, Nantong, 226001, Jiangsu, China. 15051273108@163.com., Wang F; Department of Gastrointestinal Surgery, Affiliated Nantong Clinical College of Nantong University, Nantong First People's Hospital, No. 666, Shengli Road, Nantong, 226001, Jiangsu, China. 15152890693@163.com. |
| Πηγή: | Journal of molecular histology [J Mol Histol] 2026 Jul 06; Vol. 57 (4). Date of Electronic Publication: 2026 Jul 06. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Netherlands Country of Publication: Netherlands NLM ID: 101193653 Publication Model: Electronic Cited Medium: Internet ISSN: 1567-2387 (Electronic) Linking ISSN: 15672379 NLM ISO Abbreviation: J Mol Histol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Dordrecht, The Netherlands : Springer Netherlands Original Publication: Dordrecht, The Netherlands : Kluwer Academic Publishers, 2004- |
| Ιατρικοί όροι (MeSH): | Stomach Neoplasms*/pathology , Stomach Neoplasms*/genetics , Stomach Neoplasms*/metabolism , Apoptosis*/genetics , alpha Karyopherins*/genetics , alpha Karyopherins*/metabolism , beta Catenin*/metabolism , Epithelial-Mesenchymal Transition*/genetics , Cell Cycle Checkpoints*/genetics , Signal Transduction* , Gene Knockdown Techniques*, Cell Proliferation/genetics ; Cell Movement/genetics ; Humans ; Cell Line, Tumor ; Animals ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Mice ; Neoplasm Metastasis ; Female ; Mice, Nude |
| Περίληψη: | Karyopherin subunit alpha 2 (KPNA2) has been implicated in a variety of human diseases, particularly cancer. This study aimed to elucidate the role of KPNA2 in the development and progression of gastric cancer (GC). Bioinformatics analyses revealed that KPNA2 expression was significantly higher in GC tissues, and qRT-PCR, western blotting, and immunohistochemistry subsequently validated these findings. To establish a clearer connection between bioinformatics findings and functional validation, in vitro experiments were performed in GC cell lines, in which silencing of KPNA2 significantly inhibited cell proliferation, migration, and invasion. These inhibitory effects were further confirmed in mouse xenograft models. KPNA2 depletion impaired DNA replication, induced S-phase cell cycle arrest, and significantly enhanced apoptosis in GC cells. Molecular analyses further demonstrated that KPNA2 downregulation suppressed β-catenin signaling pathway activation and inhibited epithelial-mesenchymal transition. These results suggest that KPNA2 facilitates GC cell proliferation, cell cycle progression, resistance to apoptosis, and metastatic behavior by activating the β-catenin/EMT axis. Therefore, KPNA2 may serve as a potential therapeutic target for gastric cancer. (© 2026. The Author(s), under exclusive licence to Springer Nature B.V.) |
| Competing Interests: | Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Ethics approval and consent to participate: The Animal Ethics Committee of Nantong University’s Medical School approved this study. Every experiment was carried out in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 8023, revised 1978) and the ARRIVE criteria. The Nantong First People’s Hospital Institutional Ethics Committee approved the current study (Approval No. 2022YKY042). |
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| Grant Information: | 2024JY005 Nantong University Special Research Fund for Clinical Medicine |
| Contributed Indexing: | Keywords: Apoptosis; Cell cycle; Gastric cancer; Karyopherin subunit alpha 2 (KPNA2); Proliferation; β-catenin/EMT |
| Substance Nomenclature: | 0 (alpha Karyopherins) 0 (beta Catenin) 0 (KPNA2 protein, human) |
| Entry Date(s): | Date Created: 20260706 Date Completed: 20260706 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s10735-026-10887-z |
| PMID: | 42406150 |
| Βάση Δεδομένων: | MEDLINE |
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