Academic Journal
NUP62 promotes non-small cell lung cancer progression by enhancing STAT4 nuclear translocation to upregulate CFH transcription.
| Τίτλος: | NUP62 promotes non-small cell lung cancer progression by enhancing STAT4 nuclear translocation to upregulate CFH transcription. |
|---|---|
| Συγγραφείς: | Wu M; Department of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical University, Fuyang, Anhui Province 236000, China; Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230012, China; Department of Respiratory Medicine, Anhui Public Health Clinical Center, Hefei, Anhui Province 230012, China., Wang X; Department of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical University, Fuyang, Anhui Province 236000, China., Chai Q; Department of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical University, Fuyang, Anhui Province 236000, China., Cao X; Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230012, China; Department of Respiratory Medicine, Anhui Public Health Clinical Center, Hefei, Anhui Province 230012, China., Qian K; Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230012, China; Department of Respiratory Medicine, Anhui Public Health Clinical Center, Hefei, Anhui Province 230012, China., Li Y; Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230012, China; Department of Respiratory Medicine, Anhui Public Health Clinical Center, Hefei, Anhui Province 230012, China., Zhao L; Department of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical University, Fuyang, Anhui Province 236000, China; Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230012, China; Department of Respiratory Medicine, Anhui Public Health Clinical Center, Hefei, Anhui Province 230012, China. Electronic address: yfyb10396012@fy.ahmu.edu.cn. |
| Πηγή: | Tissue & cell [Tissue Cell] 2026 Nov; Vol. 103, pp. 103691. Date of Electronic Publication: 2026 Jun 09. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Churchill Livingstone Country of Publication: Scotland NLM ID: 0214745 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-3072 (Electronic) Linking ISSN: 00408166 NLM ISO Abbreviation: Tissue Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: Edinburgh : Churchill Livingstone Original Publication: Edinburgh, Oliver & Boyd. |
| Ιατρικοί όροι (MeSH): | Carcinoma, Non-Small-Cell Lung*/metabolism , Carcinoma, Non-Small-Cell Lung*/pathology , Complement Factor H*/metabolism , Lung Neoplasms*/metabolism , Lung Neoplasms*/pathology , Membrane Glycoproteins*/metabolism , Nuclear Pore Complex Proteins*/metabolism , STAT4 Transcription Factor*/metabolism, Cell Nucleus/metabolism ; Lung/pathology ; Female ; Humans ; Male ; Mice ; Middle Aged ; A549 Cells ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Mice, Inbred BALB C ; Mice, Nude ; Animals |
| Περίληψη: | Globally, non-small cell lung cancer (NSCLC) accounts for a substantial proportion of cancer deaths. Nucleoporin 62 (NUP62), a key component of the nuclear pore complex, is tightly linked to cellular functions and tumorigenesis. This study demonstrated that NUP62 was significantly overexpressed in NSCLC tissues. Preliminary investigation conducted via the Kaplan-Meier Plotter database suggested that such aberrant overexpression correlates with poor clinical outcomes in NSCLC cases. For the purpose of studying the loss- and gain-of-function characteristics of NUP62 among NSCLC cell lines, we established NUP62-overexpressing and NUP62-knockdown cell lines using lentivirus-mediated gene delivery and RNA interference, respectively. Further experiments revealed that NUP62 overexpression elevated NSCLC cell proliferation, migration, and invasion capabilities, while NUP62 knockdown attenuated these malignant phenotypes. Mechanistically, upon phosphorylation, signal transducer and activator of transcription 4 (STAT4) migrates into the nucleus and modulates gene expression. STAT4 is also a transcription factor for complement factor H (CFH), which enables cancer cells to evade complement-mediated immune attack. In this study, NUP62 overexpression dramatically increased phosphorylated STAT4 (p-STAT4) in the nucleus, thus upregulating the transcription of CFH. Rescue assays uncovered that although increased STAT4 expression enhanced proliferative, migratory and invasive abilities of NSCLC cells, such malignant properties could be notably abolished by NUP62 depletion. In conclusion, abrogating of the NUP62-STAT4-CFH axis diminishes the neoplastic phenotypes of NSCLC cells. This finding supplies reliable molecular evidence for drug target screening and clinical prognosis evaluation of NSCLC. (Copyright © 2026 Elsevier Ltd. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. |
| Contributed Indexing: | Keywords: Complement factor H; Malignant phenotype; Non-small cell lung cancer; Nucleoporin 62; Signal transducer and activator of transcription 4 |
| Substance Nomenclature: | 0 (CFH protein, human) 80295-65-4 (Complement Factor H) 0 (Membrane Glycoproteins) 0 (Nuclear Pore Complex Proteins) 0 (nuclear pore protein p62) 0 (STAT4 protein, human) 0 (STAT4 Transcription Factor) |
| Entry Date(s): | Date Created: 20260613 Date Completed: 20260916 Latest Revision: 20261008 |
| Update Code: | 20261009 |
| DOI: | 10.1016/j.tice.2026.103691 |
| PMID: | 42288007 |
| Βάση Δεδομένων: | MEDLINE |
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