NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner
Introduction: Condensin, a family of structural maintenance of chromosome complexes, has been shown to regulate chromosome compaction and segregation during mitosis. NCAPD3, a HEAT-repeat subunit of condensin II, plays a dominant role in condensin-mediated chromosome dynamics but remains unexplored...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Journal of Advanced Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000869 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832595782607306752 |
|---|---|
| author | Tiange Lu Juan Yang Yiqing Cai Mengfei Ding Zhuoya Yu Xiaosheng Fang Xiangxiang Zhou Xin Wang |
| author_facet | Tiange Lu Juan Yang Yiqing Cai Mengfei Ding Zhuoya Yu Xiaosheng Fang Xiangxiang Zhou Xin Wang |
| author_sort | Tiange Lu |
| collection | DOAJ |
| description | Introduction: Condensin, a family of structural maintenance of chromosome complexes, has been shown to regulate chromosome compaction and segregation during mitosis. NCAPD3, a HEAT-repeat subunit of condensin II, plays a dominant role in condensin-mediated chromosome dynamics but remains unexplored in lymphoma. Objectives: The study aims to unravel the molecular function and mechanism of NCAPD3 in diffuse large B-cell lymphoma (DLBCL). Methods: The expression and clinical significance of NCAPD3 were assessed in public database and clinical specimens. Chromosome spreads, co-immunoprecipitation (co-IP), mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) assays were conducted to untangle the role and mechanism of NCAPD3 in DLBCL. Results: NCAPD3 was highly expressed in DLBCL, correlated with poor prognosis. NCAPD3 deficiency impeded cell proliferation, induced apoptosis and increased the chemosensitivity. Instead, NCAPD3 overexpression facilitated cell proliferation. In vivo experiments further indicated targeting NCAPD3 suppressed tumor growth. Noteworthily, NCAPD3 deficiency disturbed the mitosis, triggering the formation of aneuploids. To reveal the function of NCAPD3 in DLBCL, chromosome spreads were conducted, presenting that chromosomes became compact upon NCAPD3 overexpression, instead, loose, twisted and lacking axial rigidity upon NCAPD3 absence. Meanwhile, the classical transcription-activated marker, H3K4 trimethylation, was found globally upregulated after NCAPD3 knockout, suggesting that NCAPD3 might participate in chromatin remodeling and transcription regulation. MS revealed NCAPD3 could interact with transcription factor, TFII I. Further co-IP and ChIP assays verified NCAPD3 could be anchored at the promoter of SIRT1 by TFII I and then supported the transcription of SIRT1 via recognizing H3K9 monomethylation (H3K9me1) on SIRT1 promoter. Function reversion assay verified the oncogenic role of NCAPD3 in DLBCL was partially mediated by SIRT1. Conclusion: This study demonstrated that dysregulation of NCAPD3 could disturb chromosome compaction and segregation and regulate the transcription activity of SIRT1 in an H3K9me1-dependent manner, which provided novel insights into targeted strategy for DLBCL. |
| format | Article |
| id | doaj-art-9df66c5f70314159862aa120e1666c05 |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-9df66c5f70314159862aa120e1666c052025-01-18T05:04:21ZengElsevierJournal of Advanced Research2090-12322025-02-0168163178NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent mannerTiange Lu0Juan Yang1Yiqing Cai2Mengfei Ding3Zhuoya Yu4Xiaosheng Fang5Xiangxiang Zhou6Xin Wang7Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, ChinaDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, ChinaDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, ChinaDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, ChinaDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Taishan Scholars Program of Shandong Province, Jinan, Shandong 250021, China; Branch of National Clinical Research Center for Hematologic Diseases, Jinan, Shandong 250021, China; National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 251006, China; Corresponding authors at: Department of Hematology, Shandong Provincial Hospital, Shandong University, No. 324, Jingwu Road, Jinan, Shandong 250021, China.Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Taishan Scholars Program of Shandong Province, Jinan, Shandong 250021, China; Branch of National Clinical Research Center for Hematologic Diseases, Jinan, Shandong 250021, China; National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 251006, China; Corresponding authors at: Department of Hematology, Shandong Provincial Hospital, Shandong University, No. 324, Jingwu Road, Jinan, Shandong 250021, China.Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Taishan Scholars Program of Shandong Province, Jinan, Shandong 250021, China; Branch of National Clinical Research Center for Hematologic Diseases, Jinan, Shandong 250021, China; National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 251006, China; Corresponding authors at: Department of Hematology, Shandong Provincial Hospital, Shandong University, No. 324, Jingwu Road, Jinan, Shandong 250021, China.Introduction: Condensin, a family of structural maintenance of chromosome complexes, has been shown to regulate chromosome compaction and segregation during mitosis. NCAPD3, a HEAT-repeat subunit of condensin II, plays a dominant role in condensin-mediated chromosome dynamics but remains unexplored in lymphoma. Objectives: The study aims to unravel the molecular function and mechanism of NCAPD3 in diffuse large B-cell lymphoma (DLBCL). Methods: The expression and clinical significance of NCAPD3 were assessed in public database and clinical specimens. Chromosome spreads, co-immunoprecipitation (co-IP), mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) assays were conducted to untangle the role and mechanism of NCAPD3 in DLBCL. Results: NCAPD3 was highly expressed in DLBCL, correlated with poor prognosis. NCAPD3 deficiency impeded cell proliferation, induced apoptosis and increased the chemosensitivity. Instead, NCAPD3 overexpression facilitated cell proliferation. In vivo experiments further indicated targeting NCAPD3 suppressed tumor growth. Noteworthily, NCAPD3 deficiency disturbed the mitosis, triggering the formation of aneuploids. To reveal the function of NCAPD3 in DLBCL, chromosome spreads were conducted, presenting that chromosomes became compact upon NCAPD3 overexpression, instead, loose, twisted and lacking axial rigidity upon NCAPD3 absence. Meanwhile, the classical transcription-activated marker, H3K4 trimethylation, was found globally upregulated after NCAPD3 knockout, suggesting that NCAPD3 might participate in chromatin remodeling and transcription regulation. MS revealed NCAPD3 could interact with transcription factor, TFII I. Further co-IP and ChIP assays verified NCAPD3 could be anchored at the promoter of SIRT1 by TFII I and then supported the transcription of SIRT1 via recognizing H3K9 monomethylation (H3K9me1) on SIRT1 promoter. Function reversion assay verified the oncogenic role of NCAPD3 in DLBCL was partially mediated by SIRT1. Conclusion: This study demonstrated that dysregulation of NCAPD3 could disturb chromosome compaction and segregation and regulate the transcription activity of SIRT1 in an H3K9me1-dependent manner, which provided novel insights into targeted strategy for DLBCL.http://www.sciencedirect.com/science/article/pii/S2090123224000869CondensinNCAPD3Chromatin conformationSIRT1H3K9 monomethylationDiffuse large B-cell lymphoma |
| spellingShingle | Tiange Lu Juan Yang Yiqing Cai Mengfei Ding Zhuoya Yu Xiaosheng Fang Xiangxiang Zhou Xin Wang NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner Journal of Advanced Research Condensin NCAPD3 Chromatin conformation SIRT1 H3K9 monomethylation Diffuse large B-cell lymphoma |
| title | NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner |
| title_full | NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner |
| title_fullStr | NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner |
| title_full_unstemmed | NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner |
| title_short | NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner |
| title_sort | ncapd3 promotes diffuse large b cell lymphoma progression through modulating sirt1 expression in an h3k9 monomethylation dependent manner |
| topic | Condensin NCAPD3 Chromatin conformation SIRT1 H3K9 monomethylation Diffuse large B-cell lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000869 |
| work_keys_str_mv | AT tiangelu ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT juanyang ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT yiqingcai ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT mengfeiding ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT zhuoyayu ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT xiaoshengfang ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT xiangxiangzhou ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner AT xinwang ncapd3promotesdiffuselargebcelllymphomaprogressionthroughmodulatingsirt1expressioninanh3k9monomethylationdependentmanner |