Academic Journal
YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance.
| Τίτλος: | YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance. |
|---|---|
| Συγγραφείς: | Geng ZH; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.; Shanghai Collaborative Innovation Center of Endoscopy, 200032, Shanghai, China., Du JX; Department of General Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China., Chen YD; Department of General Surgery, Zhongshan Hospital, Fudan University (Xiamen Branch), 361004, Xiamen, Fujian, China., Fu PY; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.; Shanghai Collaborative Innovation Center of Endoscopy, 200032, Shanghai, China., Zhou PH; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China. zhou.pinghong@zs-hospital.sh.cn.; Shanghai Collaborative Innovation Center of Endoscopy, 200032, Shanghai, China. zhou.pinghong@zs-hospital.sh.cn., Qin WZ; Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China. qin.wenzheng@zs-hospital.sh.cn.; Shanghai Collaborative Innovation Center of Endoscopy, 200032, Shanghai, China. qin.wenzheng@zs-hospital.sh.cn., Luo YH; Department of General Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China. luo.yihong@zs-hospital.sh.cn. |
| Πηγή: | Cancer cell international [Cancer Cell Int] 2024 Feb 12; Vol. 24 (1), pp. 71. Date of Electronic Publication: 2024 Feb 12. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BioMed Central Country of Publication: England NLM ID: 101139795 Publication Model: Electronic Cited Medium: Print ISSN: 1475-2867 (Print) Linking ISSN: 14752867 NLM ISO Abbreviation: Cancer Cell Int Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2001- |
| Περίληψη: | Objective: Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1. Design: Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments. Results: Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues. Conclusions: Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes. (© 2024. The Author(s).) |
| References: | Gastric Cancer. 2017 Mar;20(2):217-225. (PMID: 26897166) Cancer Manag Res. 2021 Feb 11;13:1333-1342. (PMID: 33603479) Genomics. 2009 Feb;93(2):152-8. (PMID: 18950698) Mol Cell. 2015 Jul 16;59(2):298-308. (PMID: 26166707) Cancer Immunol Res. 2019 Apr;7(4):630-643. (PMID: 30755403) Gastroenterology. 2017 Jan;152(1):232-242.e4. (PMID: 27639803) Nat Commun. 2013;4:2612. (PMID: 24113773) Cancer Discov. 2022 Jul 6;12(7):1718-1741. (PMID: 35412588) Nucleic Acids Res. 2020 Jul 2;48(W1):W509-W514. (PMID: 32442275) Theranostics. 2020 Mar 4;10(9):4183-4200. (PMID: 32226547) Gastric Cancer. 2021 May;24(3):642-654. (PMID: 33544270) J Clin Oncol. 2013 Sep 10;31(26):3219-25. (PMID: 23918952) Oxid Med Cell Longev. 2022 May 11;2022:9925919. (PMID: 35602105) J Clin Oncol. 2016 May 1;34(13):1448-54. (PMID: 26884585) Cancer Res. 2017 Nov 1;77(21):e108-e110. (PMID: 29092952) Gastric Cancer. 2021 Jan;24(1):1-21. (PMID: 32060757) Carcinogenesis. 2020 Jul 14;41(7):950-960. (PMID: 31587040) Nucleic Acids Res. 2021 Jan 8;49(D1):D916-D923. (PMID: 33270111) Blood. 2020 Aug 6;136(6):726-739. (PMID: 32374849) Cancer Discov. 2021 Mar;11(3):678-695. (PMID: 33203734) Acta Pharm Sin B. 2022 Feb;12(2):692-707. (PMID: 35256940) Drug Resist Updat. 2019 Mar;43:10-28. (PMID: 31005030) Front Pharmacol. 2018 Nov 22;9:1371. (PMID: 30524291) CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338) J Exp Clin Cancer Res. 2016 May 25;35:84. (PMID: 27225481) Int J Cancer. 2018 Aug 1;143(3):460-465. (PMID: 29322514) Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792) Cell. 2014 Jan 16;156(1-2):317-331. (PMID: 24439385) Cancer Cell. 2016 Sep 12;30(3):444-458. (PMID: 27569582) Toxicol In Vitro. 2021 Aug;74:105152. (PMID: 33771646) Biochem Biophys Res Commun. 2015 Dec 25;468(4):525-32. (PMID: 26482853) Br J Surg. 2015 Jun;102(7):813-25. (PMID: 25866938) J Cell Commun Signal. 2021 Jun;15(2):251-267. (PMID: 33620645) Nucleic Acids Res. 2018 Jan 4;46(D1):D380-D386. (PMID: 29087512) Pathol Oncol Res. 2020 Oct;26(4):2813-2815. (PMID: 31828582) J Hepatol. 2003 Nov;39(5):742-8. (PMID: 14568256) Lancet Oncol. 2021 Nov;22(11):1609-1617. (PMID: 34624252) Cell Mol Biol Lett. 2021 Apr 1;26(1):12. (PMID: 33794762) Exp Dermatol. 2022 Apr;31(4):556-566. (PMID: 34758170) Antiviral Res. 2020 Feb;174:104695. (PMID: 31846633) Mol Cell Biol. 1999 Oct;19(10):7237-44. (PMID: 10490658) Genome Biol. 2016 Aug 22;17(1):174. (PMID: 27549193) Hepatology. 2017 Dec;66(6):1920-1933. (PMID: 28732118) Cancer Immunol Immunother. 2020 Sep;69(9):1781-1799. (PMID: 32347357) Nature. 2015 Apr 2;520(7545):57-62. (PMID: 25799988) Free Radic Biol Med. 2021 Jan;162:339-352. (PMID: 33157209) J Exp Clin Cancer Res. 2021 May 15;40(1):171. (PMID: 33992102) Cancer Lett. 2020 Jul 10;482:90-101. (PMID: 32278016) |
| Grant Information: | 82003083 Natural Science Foundation of China |
| Contributed Indexing: | Keywords: Apatinib; Ferroptosis; Gastric cancer; YY1; p53 |
| Entry Date(s): | Date Created: 20240212 Latest Revision: 20240215 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10863212 |
| DOI: | 10.1186/s12935-024-03262-z |
| PMID: | 38347631 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!