YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer
ABSTRACT Background Gastric cancer (GC) is an important cause of death. Molecular targeted therapy and immunotherapy are progressing rapidly. It is very important to explore the pathogenesis pathways of GC and provide strong support for its treatment. However, the mechanism of occurrence and develop...
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2025-01-01
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| Online Access: | https://doi.org/10.1002/cam4.70611 |
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| author | Yangyuan Huang Shihao Liang Liping Li Qingyu Zeng Bin Li |
| author_facet | Yangyuan Huang Shihao Liang Liping Li Qingyu Zeng Bin Li |
| author_sort | Yangyuan Huang |
| collection | DOAJ |
| description | ABSTRACT Background Gastric cancer (GC) is an important cause of death. Molecular targeted therapy and immunotherapy are progressing rapidly. It is very important to explore the pathogenesis pathways of GC and provide strong support for its treatment. However, the mechanism of occurrence and development of GC is still unclear. Methods Online databases and immunohistochemistry (IHC) of clinical samples were used to analyze the differential expression of YTHDF1 in the GC and nearby tissues, and its effect on survival prognosis. In vitro experimental study of GC, other mechanisms and functional analyses were specifically designed and performed too. Results Online data and clinical samples analysis showed that the expression of YTHDF1 in GC was markedly elevated compared to surrounding tissues. Higher YTHDF1 levels were correlated with worse survival outcomes. Analysis of correlation with clinical parameters showed that the expression level of YTHDF1 exhibited a favorable correlation with lymphatic metastases, as well as with PD‐1 and PD‐L1 levels. In vitro studies of YTHDF1 overexpression have demonstrated its ability to enhance GC cell growth and migration while inhibiting apoptosis. Based on our results, RELA is a downstream target of YTHDF1, and YTHDF1 triggers the NF‐κB signaling pathway by regulating RELA translation. Conclusion In comparison to adjacent tissues, GC exhibits significantly elevated YTHDF1 expression. Increased YTHDF1 expression in the GC is correlated with decreased patient survival. Lymph node metastasis and the expression of PD‐1 and PD‐L1 are positively correlated with YTHDF1 levels. YTHDF1 inhibits apoptosis while promoting the migration and proliferation of GC. Additionally, it stimulates the NF‐κB pathway and controls the translation of RELA. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-d3f3cd35707842aca0a4cf35d0bfc4952025-01-24T08:46:07ZengWileyCancer Medicine2045-76342025-01-01142n/an/a10.1002/cam4.70611YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric CancerYangyuan Huang0Shihao Liang1Liping Li2Qingyu Zeng3Bin Li4Department of Gastroenterology Affiliated Hospital of Guilin Medical University Guilin Guangxi People's Republic of ChinaDepartment of Gastroenterology Affiliated Hospital of Guilin Medical University Guilin Guangxi People's Republic of ChinaDepartment of Gastroenterology Affiliated Hospital of Guilin Medical University Guilin Guangxi People's Republic of ChinaDepartment of Gastroenterology Affiliated Hospital of Guilin Medical University Guilin Guangxi People's Republic of ChinaDepartment of Gastroenterology Affiliated Hospital of Guilin Medical University Guilin Guangxi People's Republic of ChinaABSTRACT Background Gastric cancer (GC) is an important cause of death. Molecular targeted therapy and immunotherapy are progressing rapidly. It is very important to explore the pathogenesis pathways of GC and provide strong support for its treatment. However, the mechanism of occurrence and development of GC is still unclear. Methods Online databases and immunohistochemistry (IHC) of clinical samples were used to analyze the differential expression of YTHDF1 in the GC and nearby tissues, and its effect on survival prognosis. In vitro experimental study of GC, other mechanisms and functional analyses were specifically designed and performed too. Results Online data and clinical samples analysis showed that the expression of YTHDF1 in GC was markedly elevated compared to surrounding tissues. Higher YTHDF1 levels were correlated with worse survival outcomes. Analysis of correlation with clinical parameters showed that the expression level of YTHDF1 exhibited a favorable correlation with lymphatic metastases, as well as with PD‐1 and PD‐L1 levels. In vitro studies of YTHDF1 overexpression have demonstrated its ability to enhance GC cell growth and migration while inhibiting apoptosis. Based on our results, RELA is a downstream target of YTHDF1, and YTHDF1 triggers the NF‐κB signaling pathway by regulating RELA translation. Conclusion In comparison to adjacent tissues, GC exhibits significantly elevated YTHDF1 expression. Increased YTHDF1 expression in the GC is correlated with decreased patient survival. Lymph node metastasis and the expression of PD‐1 and PD‐L1 are positively correlated with YTHDF1 levels. YTHDF1 inhibits apoptosis while promoting the migration and proliferation of GC. Additionally, it stimulates the NF‐κB pathway and controls the translation of RELA.https://doi.org/10.1002/cam4.70611gastric cancerNF‐kappa B signaling pathwayRELAYTHDF1 |
| spellingShingle | Yangyuan Huang Shihao Liang Liping Li Qingyu Zeng Bin Li YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer Cancer Medicine gastric cancer NF‐kappa B signaling pathway RELA YTHDF1 |
| title | YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer |
| title_full | YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer |
| title_fullStr | YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer |
| title_full_unstemmed | YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer |
| title_short | YTHDF1 Regulates RELA m6A Modification and Activates the NF‐Kappa B Signaling Pathway to Promote the Mechanism of Gastric Cancer |
| title_sort | ythdf1 regulates rela m6a modification and activates the nf kappa b signaling pathway to promote the mechanism of gastric cancer |
| topic | gastric cancer NF‐kappa B signaling pathway RELA YTHDF1 |
| url | https://doi.org/10.1002/cam4.70611 |
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