YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance
Abstract 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 G...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-024-03262-z |
| _version_ | 1827326093508476928 |
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| author | Zi-Han Geng Jun-Xian Du Yue-Da Chen Pei-Yao Fu Ping-Hong Zhou Wen-Zheng Qin Yi-Hong Luo |
| author_facet | Zi-Han Geng Jun-Xian Du Yue-Da Chen Pei-Yao Fu Ping-Hong Zhou Wen-Zheng Qin Yi-Hong Luo |
| author_sort | Zi-Han Geng |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T14:39:41Z |
| format | Article |
| id | doaj.art-5b8712f27b094bb2b6cbeee325e644ee |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-07T14:39:41Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-5b8712f27b094bb2b6cbeee325e644ee2024-03-05T20:25:39ZengBMCCancer Cell International1475-28672024-02-0124111210.1186/s12935-024-03262-zYY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistanceZi-Han Geng0Jun-Xian Du1Yue-Da Chen2Pei-Yao Fu3Ping-Hong Zhou4Wen-Zheng Qin5Yi-Hong Luo6Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan UniversityDepartment of General Surgery, Zhongshan Hospital, Fudan UniversityDepartment of General Surgery, Zhongshan Hospital, Fudan University (Xiamen Branch)Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan UniversityEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan UniversityEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan UniversityDepartment of General Surgery, Zhongshan Hospital, Fudan UniversityAbstract 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.https://doi.org/10.1186/s12935-024-03262-zGastric cancerYY1FerroptosisApatinibp53 |
| spellingShingle | Zi-Han Geng Jun-Xian Du Yue-Da Chen Pei-Yao Fu Ping-Hong Zhou Wen-Zheng Qin Yi-Hong Luo YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance Cancer Cell International Gastric cancer YY1 Ferroptosis Apatinib p53 |
| title | YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance |
| title_full | YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance |
| title_fullStr | YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance |
| title_full_unstemmed | YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance |
| title_short | YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance |
| title_sort | yy1 a key regulator inhibits gastric cancer ferroptosis and mediating apatinib resistance |
| topic | Gastric cancer YY1 Ferroptosis Apatinib p53 |
| url | https://doi.org/10.1186/s12935-024-03262-z |
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