Academic Journal
Προβολή σε EDS
Συνδεδεμένο Πλήρες Κείμενο

SERPINB5 promotes pancreatic adenocarcinoma progression through FBXO32-mediated regulation of epithelial-mesenchymal transition.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: SERPINB5 promotes pancreatic adenocarcinoma progression through FBXO32-mediated regulation of epithelial-mesenchymal transition.
Συγγραφείς: Jiang H; Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, No. 292, Beijing Road, Guandu District, Kunming, Yunnan, 650200, China., Zhang PJ; Department of Neurosurgery, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, 110840, Liaoning, China., Li W; Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, No. 292, Beijing Road, Guandu District, Kunming, Yunnan, 650200, China., Zhang HF; Department of Neurosurgery, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, 110840, Liaoning, China. zhanghf615@163.com.
Πηγή: Molecular biology reports [Mol Biol Rep] 2026 Oct 15; Vol. 53 (1). Date of Electronic Publication: 2026 Oct 15.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: Dordrecht, Boston, Reidel.
Ιατρικοί όροι (MeSH): Epithelial-Mesenchymal Transition*/genetics , Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/metabolism , Adenocarcinoma*/genetics , Adenocarcinoma*/pathology , Adenocarcinoma*/metabolism , Serpins*/genetics , Serpins*/metabolism , F-Box Proteins*/genetics , F-Box Proteins*/metabolism, Gene Expression Regulation, Neoplastic/genetics ; Cell Proliferation/genetics ; Cell Movement/genetics ; Humans ; Cell Line, Tumor ; Disease Progression ; Prognosis
Περίληψη: Background: Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignancy. This study aimed to investigate the clinical significance and biological functions of SERPINB5 in PAAD.
Methods: Differentially expressed genes were screened from the TCGA-PAAD, GSE32676, and GSE101448 datasets. The candidate gene SERPINB5 was identified using LASSO Cox regression and receiver operating characteristic (ROC) curve analysis. SERPINB5 expression in PAAD cell lines was validated via in vitro experiments. The effects of silencing SERPINB5 on cellular phenotypes and epithelial-mesenchymal transition (EMT) were assessed using CCK-8, colony formation, and Transwell assays, as well as immunofluorescence and Western blotting. Co-immunoprecipitation (Co-IP) and rescue experiments were conducted to explore the relationship between SERPINB5 and FBXO32.
Results: A risk model identified seven candidate prognostic genes, including SERPINB5. Independent single-gene ROC analysis assessed its ability to discriminate PAAD tumors from normal pancreatic tissues across three transcriptomic datasets, with areas under the curve (AUC) values of 0.851, 0.966, and 0.965. Expression analysis revealed consistently high SERPINB5 levels in both PAAD tissues and cell lines. Functional studies showed that silencing SERPINB5 inhibited PAAD cell proliferation, colony formation, migration, and invasion. Mechanistic studies indicated that SERPINB5 knockdown upregulated E-cadherin expression while downregulating Vimentin and N-cadherin levels. Co-IP experiments confirmed a physical interaction between SERPINB5 and FBXO32, and SERPINB5 knockdown resulted in reduced FBXO32 expression. Furthermore, FBXO32 overexpression reversed the malignant phenotypes and EMT-related changes caused by SERPINB5 silencing.
Conclusion: Our findings indicate that SERPINB5 may be a candidate diagnostic and prognostic marker for PAAD. Functionally, the SERPINB5/FBXO32 axis appears to promote PAAD progression, at least partly, through epithelial-mesenchymal transition regulation.
(© 2026. The Author(s), under exclusive licence to Springer Nature B.V.)
Competing Interests: Declarations. AI Disclosure Statement: In this dissertation, the author used AI tools to assist in literature retrieval and organization/diagram production/code debugging and analysis/grammar proofreading and format checking, etc. The core ideas, research design, conclusions, and innovations of the dissertation were all completed independently by the author. The author conducted a legal review and reasonable editing of the content, completed with the assistance of this tool, and I assume all legal and academic ethical responsibilities for the content of this dissertation. Competing interests: The authors declare no competing interests. Consent for publication: Not applicable. Ethics approval and consent to participate: Not applicable.
References: Luo W et al (2023) Epidemiology of pancreatic cancer: New version, new vision. Chin J Cancer Res 35(5):438–450. (PMID: 10.21147/j.issn.1000-9604.2023.05.033796995710643340)
Li Y et al (2024) Pathomic and bioinformatics analysis of clinical-pathological and genomic factors for pancreatic cancer prognosis. Sci Rep 14(1):27769. (PMID: 10.1038/s41598-024-79619-13953309111557977)
Grigorescu RR, Husar-Sburlan IA, Gheorghe C (2024) Pancreatic Cancer: Rev Risk Factors Life (Basel) 14(8):980.
Hafezi S, Saber-Ayad M, Abdel-Rahman WM (2021) Highlights on the role of KRAS mutations in reshaping the microenvironment of pancreatic adenocarcinoma. Int J Mol Sci 22(19):10219. (PMID: 10.3390/ijms221910219346385608508406)
Zhu Y-H et al (2023) Immunosuppression, immune escape, and immunotherapy in pancreatic cancer: focused on the tumor microenvironment. Cell Oncol 46(1):17–48. (PMID: 10.1007/s13402-022-00741-1)
Wang Q, Liu J, Yang Z (2025) Global, regional, and national burden of pancreatic cancer from 1990 to 2021, with projections for 25 years: a systematic analysis for the Global Burden of Disease Study 2021. Eur J Cancer Prev 34(6):493–503. (PMID: 10.1097/CEJ.000000000000094239718214)
Bray F et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229–263. (PMID: 38572751)
Peng C, Oberstein PE (2025) Emerging Therapeutic Approaches to Pancreatic Adenocarcinoma: Advances and Future Directions. Current Treatment Options in Oncology 1–25.
Mannucci A, Goel A (2025) Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future. A Cancer Journal for Clinicians, CA.
Heit C et al (2013) Update of the human and mouse SERPIN gene superfamily. Hum Genomics 7(1):22. (PMID: 10.1186/1479-7364-7-22241720143880077)
Sun Y, Sheshadri N, Zong WX (2017) SERPINB3 and B4: From biochemistry to biology. Semin Cell Dev Biol 62:170–177. (PMID: 10.1016/j.semcdb.2016.09.00527637160)
Tian C et al (2020) Cancer Cell-Derived Matrisome Proteins Promote Metastasis in Pancreatic Ductal Adenocarcinoma. Cancer Res 80(7):1461–1474. (PMID: 10.1158/0008-5472.CAN-19-2578320295507127978)
Bose S et al (2025) From enzyme to predictors: Serine proteases in cancer diagnosis and prognosis, in Pathophysiological Aspects of Proteases in Cancer. Elsevier, pp 223–237.
Maass N et al (2001) Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res 7(4):812–817. (PMID: 11309327)
Liu B-X et al (2024) SERPINB5 promotes colorectal cancer invasion and migration by promoting EMT and angiogenesis via the TNF-α/NF-κB pathway. Int Immunopharmacol 131:111759. (PMID: 10.1016/j.intimp.2024.11175938460302)
Lidström T (2022) Immunosuppressive and metastasis-promoting matrisome proteins in pancreatic cancer: the role of galectin 4 and SERPINB5. Umeå University.
Nakayama T et al (2018) Assessment of suitable reference genes for RT–qPCR studies in chronic rhinosinusitis. Sci Rep 8(1):1568. (PMID: 10.1038/s41598-018-19834-9293716065785529)
Xiang Y et al (2021) Comparison of the sensitivity of Western blotting between PVDF and NC membranes. Sci Rep 11(1):12022. (PMID: 10.1038/s41598-021-91521-8341036208187435)
Lei K-F et al (2011) SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells. Oncol Rep 26(5):1115–1120. (PMID: 21725612)
Zhang Q et al (2025) Metabolic and immune crosstalk between cancer-associated fibroblasts and pancreatic cancer cells. J Translational Med 23(1):1118. (PMID: 10.1186/s12967-025-07164-0)
Wang H et al (2022) Identification of prognostic genes in the pancreatic adenocarcinoma immune microenvironment by integrated bioinformatics analysis. Cancer Immunol Immunother 71(7):1757–1769. (PMID: 10.1007/s00262-021-03110-334854950)
Yang J et al (2022) COL17A1 facilitates tumor growth and predicts poor prognosis in pancreatic cancer. Biochem Biophys Res Commun 632:1–9. (PMID: 10.1016/j.bbrc.2022.09.04936191371)
Liu N et al (2021) High matrix metalloproteinase 28 expression is associated with poor prognosis in pancreatic adenocarcinoma. OncoTargets therapy 14:4391–4406.
Jiang Y et al (2025) PUS7 promotes the progression of pancreatic cancer by interacting ANLN to activate MYC pathway. Mol Cell Biochem 480(7):4401–4415.
He X et al (2023) SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial-mesenchymal transition (EMT) in lung adenocarcinoma. Thorac Cancer 14(23):2275–2287. (PMID: 10.1111/1759-7714.1501337424293)
Zeng S et al (2025) The paradoxical role of SERPINB5 in gastrointestinal cancers: oncogene or tumor suppressor? Mol Biol Rep 52(1):188. (PMID: 10.1007/s11033-025-10293-w39899168)
Meng Z-S et al (2025) Inhibition of the SERPINB5/HSP90AA1 axis restrains the proliferation and invasion of rectal cancer. World J Gastroenterol 31(11):103412. (PMID: 10.3748/wjg.v31.i11.1034124012426211924014)
Mahananda B et al (2021) SERPINB5 genetic variants rs2289519 and rs2289521 are significantly associated with gallbladder cancer risk. DNA Cell Biol 40(5):706–712. (PMID: 10.1089/dna.2021.005633691472)
Ji T et al (2021) PADI1 contributes to EMT in PAAD by activating the ERK1/2-p38 signaling pathway. J Gastrointest Oncol 12(3):1180. (PMID: 10.21037/jgo-21-283342955668261327)
Ghafoor S et al (2025) Molecular Mechanisms Regulating Epithelial Mesenchymal Transition (EMT) to Promote Cancer Progression. Int J Mol Sci 26(9):4364. (PMID: 10.3390/ijms260943644036260012072817)
Ji Q et al (2023) PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer. Int J Biol Sci 19(6):1894. (PMID: 10.7150/ijbs.767563706342510092766)
He R-Z et al (2023) ADAMTS12 promotes migration and epithelial-mesenchymal transition and predicts poor prognosis for pancreatic cancer, vol 22. Hepatobiliary & Pancreatic Diseases International, pp 169–178. 2.
Oshi M et al (2021) Annexin A1 expression is associated with Epithelial–Mesenchymal Transition (EMT), cell proliferation, prognosis, and drug response in pancreatic cancer. Cells 10(3):653. (PMID: 10.3390/cells10030653338041488000658)
Dai M et al (2025) F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies. Front Immunol 16:1596344. (PMID: 10.3389/fimmu.2025.15963444053486712174096)
Wu J et al (2024) FBXO32-mediated degradation of PTEN promotes lung adenocarcinoma progression. Cell Death Dis 15(4):282. (PMID: 10.1038/s41419-024-06635-43864321511032391)
Rao X-H et al (2025) FBXO32 promotes gastric cancer progression by regulating NME1. Translational Cancer Res 14(6):3520–3531. (PMID: 10.21037/tcr-2024-2426)
Wang H et al (2021) Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk. Mol Carcinog 60(10):661–670. (PMID: 10.1002/mc.23331341976558475729)
Su D et al (2024) FBXO32 stimulates protein synthesis to drive pancreatic cancer progression and metastasis. Cancer Res 84(16):2607–2625. (PMID: 10.1158/0008-5472.CAN-23-363838775804)
Zhou H et al (2017) FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation. Oncogene 36(23):3312–3321. (PMID: 10.1038/onc.2016.479280683195926769)
Chou JL et al (2010) Promoter hypermethylation of FBXO32, a novel TGF-beta/SMAD4 target gene and tumor suppressor, is associated with poor prognosis in human ovarian cancer. Lab Invest 90(3):414–425. (PMID: 10.1038/labinvest.2009.138200659492829100)
Sakharkar MK et al (2021) Key drug-targeting genes in pancreatic ductal adenocarcinoma. Genes Cancer 12:12–24. (PMID: 10.18632/genesandcancer.210338841028045979)
Grant Information: 2023MY007 Xing Dian Talent Support Program
Contributed Indexing: Keywords: FBXO32; SERPINB5; Epithelial-mesenchymal transition; Malignant progression; Pancreatic adenocarcinoma
Substance Nomenclature: 0 (SERPIN-B5)
0 (Serpins)
0 (F-Box Proteins)
Entry Date(s): Date Created: 20261015 Date Completed: 20261015 Latest Revision: 20261015
Update Code: 20261016
DOI: 10.1007/s11033-026-12945-x
PMID: 42878980
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1573-4978
DOI:10.1007/s11033-026-12945-x