HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer
BackgroundThe histone chaperone Holliday Junction Recognition Protein (HJURP) has been associated with multiple types of cancers, but its role in GC is not yet fully understood. Considering its functions in centromere stability and DNA repair, investigating HJURP’s role in GC may offer novel therape...
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Frontiers Media S.A.
2025-04-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1566293/full |
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| author | Xu Li Xu Li Xiwen Li Yanlin Ren Ling Wang Zehao Mao Shikun Gao Shikun Gao Peng Ma Junjie Chen Junjie Chen |
| author_facet | Xu Li Xu Li Xiwen Li Yanlin Ren Ling Wang Zehao Mao Shikun Gao Shikun Gao Peng Ma Junjie Chen Junjie Chen |
| author_sort | Xu Li |
| collection | DOAJ |
| description | BackgroundThe histone chaperone Holliday Junction Recognition Protein (HJURP) has been associated with multiple types of cancers, but its role in GC is not yet fully understood. Considering its functions in centromere stability and DNA repair, investigating HJURP’s role in GC may offer novel therapeutic perspectives.MethodsHJURP expression was examined in a dataset comprising TCGA-STAD samples and an internal group of GC patients, utilizing RNA sequencing and Western blot techniques. Functional experiments were carried out on the AGS and HGC-27 GC cell lines. The expression levels of HJURP, MYC, and Topoisomerase II alpha (TOP2A) were assessed via quantitative real-time PCR and Western blot. Proliferation rates of the cells were determined through EdU, CCK-8, and colony formation assays.ResultsCompared to adjacent normal tissues, HJURP expression was notably increased in GC tissues, a finding consistent across both the TCGA-STAD database and our internal patient group. Silencing HJURP markedly reduced GC cell growth and chemoresistance. Mechanistically, HJURP enhanced MYC stability, which in turn promoted TOP2A transcription. Rescue experiments confirmed that overexpression of TOP2A alters proliferation and chemoresistance of GC cells with HJURP knockdown, indicating the dependency of this axis on MYC activity.ConclusionOur study demonstrates that HJURP is critical for promoting GC proliferation and chemoresistance through the regulation of the MYC/TOP2A transcriptional network. Targeting HJURP might offer a novel therapeutic avenue for GC, necessitating further exploration of its clinical potential. This work underscores the value of investigating histone chaperones as potential targets in cancer treatment. |
| format | Article |
| id | doaj-art-b266eefeae024c3192dc865ac0a415d9 |
| institution | DOAJ |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-b266eefeae024c3192dc865ac0a415d92025-08-20T03:09:09ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-04-011210.3389/fmolb.2025.15662931566293HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancerXu Li0Xu Li1Xiwen Li2Yanlin Ren3Ling Wang4Zehao Mao5Shikun Gao6Shikun Gao7Peng Ma8Junjie Chen9Junjie Chen10Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, ChinaClinical Medical Research Center, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Central Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, ChinaDepartment of Labor Hygiene and Occupational Disease Prevention and Control, Nantong Center for Disease Control and Prevention, Nantong, ChinaDepartment of Hematology, Affiliated Hospital 2 of Nantong University, Nantong, ChinaClinical Medical Research Center, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, ChinaClinical Medical Research Center, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, ChinaClinical Medical Research Center, Affiliated Hospital of Nantong University, Nantong, ChinaNantong Key Laboratory of Gastrointestinal Oncology, Affiliated Hospital of Nantong University, Nantong, ChinaBackgroundThe histone chaperone Holliday Junction Recognition Protein (HJURP) has been associated with multiple types of cancers, but its role in GC is not yet fully understood. Considering its functions in centromere stability and DNA repair, investigating HJURP’s role in GC may offer novel therapeutic perspectives.MethodsHJURP expression was examined in a dataset comprising TCGA-STAD samples and an internal group of GC patients, utilizing RNA sequencing and Western blot techniques. Functional experiments were carried out on the AGS and HGC-27 GC cell lines. The expression levels of HJURP, MYC, and Topoisomerase II alpha (TOP2A) were assessed via quantitative real-time PCR and Western blot. Proliferation rates of the cells were determined through EdU, CCK-8, and colony formation assays.ResultsCompared to adjacent normal tissues, HJURP expression was notably increased in GC tissues, a finding consistent across both the TCGA-STAD database and our internal patient group. Silencing HJURP markedly reduced GC cell growth and chemoresistance. Mechanistically, HJURP enhanced MYC stability, which in turn promoted TOP2A transcription. Rescue experiments confirmed that overexpression of TOP2A alters proliferation and chemoresistance of GC cells with HJURP knockdown, indicating the dependency of this axis on MYC activity.ConclusionOur study demonstrates that HJURP is critical for promoting GC proliferation and chemoresistance through the regulation of the MYC/TOP2A transcriptional network. Targeting HJURP might offer a novel therapeutic avenue for GC, necessitating further exploration of its clinical potential. This work underscores the value of investigating histone chaperones as potential targets in cancer treatment.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1566293/fullgastric cancerHJURPMYC/TOP2Aproliferationchemoresistance |
| spellingShingle | Xu Li Xu Li Xiwen Li Yanlin Ren Ling Wang Zehao Mao Shikun Gao Shikun Gao Peng Ma Junjie Chen Junjie Chen HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer Frontiers in Molecular Biosciences gastric cancer HJURP MYC/TOP2A proliferation chemoresistance |
| title | HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer |
| title_full | HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer |
| title_fullStr | HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer |
| title_full_unstemmed | HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer |
| title_short | HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer |
| title_sort | hjurp modulates cell proliferation and chemoresistance via the myc top2a transcriptional axis in gastric cancer |
| topic | gastric cancer HJURP MYC/TOP2A proliferation chemoresistance |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1566293/full |
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