MAD2L2, a key regulator in ovarian cancer and promoting tumor progression
Raw Text
Search in PubMed
Search in NLM Catalog
Add to Search
.
2024 Jan 2;14(1):130.
doi: 10.1038/s41598-023-50744-7.
Kejun Xu  1 ,
Xiaojiao Zheng  1 ,
Hongyan Shi  1 ,
Jilan Ou  1 ,
Huiqing Ding  2
Expand
Affiliations
1 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China.
2 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China. 1209256240@qq.com.
PMID: 38167649
PMCID: PMC10761867
DOI: 10.1038/s41598-023-50744-7
Free PMC article
Kejun Xu  et al.
Sci Rep .
2024 .
Free PMC article
Show details
Display options
Format
Search in PubMed
Search in NLM Catalog
Add to Search
.
2024 Jan 2;14(1):130.
doi: 10.1038/s41598-023-50744-7.
Authors
Kejun Xu  1 ,
Xiaojiao Zheng  1 ,
Hongyan Shi  1 ,
Jilan Ou  1 ,
Huiqing Ding  2
Affiliations
1 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China.
2 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China. 1209256240@qq.com.
PMID: 38167649
PMCID: PMC10761867
DOI: 10.1038/s41598-023-50744-7
Cite
Display options
Format
Abstract
Ovarian cancer (OVCA), a prevalent gynecological malignancy, ranks as the fourth most common cancer among women. Mitotic Arrest Deficient 2 Like 2 (MAD2L2), a chromatin-binding protein and a component of DNA polymerase ζ, has been previously identified as an inhibitor of tumor growth in colorectal cancer. However, the roles of MAD2L2 in OVCA, including its expression, impact, and prognostic significance, remain unclear. We employed bioinformatics tools, Cox Regression analysis, and in vitro cell experiments to investigate its biological functions. Our findings reveal that MAD2L2 typically undergoes genomic alterations, such as amplifications and deep deletions. Moreover, we observed an overexpression of MAD2L2 mRNA in OVCA patients, correlating with reduced survival rates, particularly in those with Grade IV tumors. Furthermore, analysis of mRNA biofunctions indicated that MAD2L2 is predominantly localized in the organellar ribosome, engaging mainly in NADH dehydrogenase activity. This was deduced from the results of gene ontology enrichment analysis, which also identified its role as a structural constituent in mitochondrial translation elongation. These findings were corroborated by KEGG pathway analysis, further revealing MAD2L2's involvement in tumor metabolism and the cell death process. Notably, MAD2L2 protein expression showed significant associations with various immune cells, including CD4+T cells, CD8+T cells, B cells, natural killer cells, and Myeloid dendritic cells. Additionally, elevated levels of MAD2L2 were found to enhance cell proliferation and migration in OVCA cells. The upregulation of MAD2L2 also appears to inhibit the ferroptosis process, coinciding with increased mTOR signaling activity in these cells. Our study identifies MAD2L2 as a novel regulator in ovarian tumor progression and offers new insights for treating OVCA.
© 2024. The Author(s).
PubMed Disclaimer
Conflict of interest statement
The authors declare no competing interests.
Figures
Figure 1
The gene expression of MAD2L2…
Figure 1
The gene expression of MAD2L2 in pan-cancer and survival time of five common…
Figure 2
The clinical feature of MAD2L2…
Figure 2
The clinical feature of MAD2L2 in OVCA patients. ( A ) The different…
Figure 3
The gene alteration of MAD2L2…
Figure 3
The gene alteration of MAD2L2 in OVCA. ( A , B ) The…
Figure 4
The gene enrichment analysis of…
Figure 4
The gene enrichment analysis of MAD2L2. The enrichment analysis of MAD2L2. ( A…
Figure 5
Protein level expression of MAD2L2…
Figure 5
Protein level expression of MAD2L2 in single cell analysis and tumor samples. (…
Figure 6
Overexpressed MAD2L2 promotes proliferation and…
Figure 6
Overexpressed MAD2L2 promotes proliferation and the survival of OVCA cell lines, and overexpressed…
Figure 7
Upregulation of MAD2L2 Suppressed Ferroptosis…
Figure 7
Upregulation of MAD2L2 Suppressed Ferroptosis Process and Accompanied by mTOR Signaling activity in…
See this image and copyright information in PMC
References
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660. - DOI - PubMed
Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J.(Engl.) 2021;134(7):783–791. doi: 10.1097/CM9.0000000000001474. - DOI - PMC - PubMed
Konstantinopoulos PA, Matulonis UA. Clinical and translational advances in ovarian cancer therapy. Nat. Cancer. 2023;4(9):1239–1257. doi: 10.1038/s43018-023-00617-9. - DOI - PubMed
Norppa N, Staff S, Helminen M, et al. Improved survival after implementation of ultra-radical surgery in advanced epithelial ovarian cancer: Results from a tertiary referral center. Gynecol. Oncol. 2022;165(3):478–485. doi: 10.1016/j.ygyno.2022.03.023. - DOI - PubMed
Janos LT, Hye SC, Mark AM, et al. Phase 3, Randomized, Single-Dose, Open-Label Study to Investigate the Safetyand Efficacy of Pafolacianine Sodium Injection (OTL38) for Intraoperative Imaging of Folate Receptor Positive Ovarian Cancer. ASCO; 2021.
MeSH terms
Cell Line, Tumor Actions Search in PubMed Search in MeSH Add to Search
Cell Proliferation / genetics Actions Search in PubMed Search in MeSH Add to Search
Female Actions Search in PubMed Search in MeSH Add to Search
Humans Actions Search in PubMed Search in MeSH Add to Search
Mad2 Proteins / genetics Actions Search in PubMed Search in MeSH Add to Search
Mad2 Proteins / metabolism Actions Search in PubMed Search in MeSH Add to Search
Neoplastic Processes Actions Search in PubMed Search in MeSH Add to Search
Ovarian Neoplasms* / pathology Actions Search in PubMed Search in MeSH Add to Search
Proteins Actions Search in PubMed Search in MeSH Add to Search
RNA, Messenger / genetics Actions Search in PubMed Search in MeSH Add to Search
Substances
Proteins Actions Search in PubMed Search in MeSH Add to Search
RNA, Messenger Actions Search in PubMed Search in MeSH Add to Search
MAD2L2 protein, human Actions Search in PubMed Search in MeSH Add to Search
Mad2 Proteins Actions Search in PubMed Search in MeSH Add to Search
Related information
MedGen
Grants and funding
LQ21H160011/Natural Science Foundation of Zhejiang Province
2021KY990/Medical and Health Plan of Zhejiang
LinkOut - more resources
Full Text Sources Nature Publishing Group
Research Materials NCI CPTC Antibody Characterization Program
Miscellaneous NCI CPTAC Assay Portal
Single Line Text
Search in PubMed. Search in NLM Catalog. Add to Search. . 2024 Jan 2;14(1):130. doi: 10.1038/s41598-023-50744-7. Kejun Xu  1 , Xiaojiao Zheng  1 , Hongyan Shi  1 , Jilan Ou  1 , Huiqing Ding  2. Expand. Affiliations. 1 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China. 2 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China. 1209256240@qq.com. PMID: 38167649. PMCID: PMC10761867. DOI: 10.1038/s41598-023-50744-7. Free PMC article. Kejun Xu  et al. Sci Rep . 2024 . Free PMC article. Show details. Display options. Format. Search in PubMed. Search in NLM Catalog. Add to Search. . 2024 Jan 2;14(1):130. doi: 10.1038/s41598-023-50744-7. Authors. Kejun Xu  1 , Xiaojiao Zheng  1 , Hongyan Shi  1 , Jilan Ou  1 , Huiqing Ding  2. Affiliations. 1 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China. 2 Gynaecology and Obstetrics Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China. 1209256240@qq.com. PMID: 38167649. PMCID: PMC10761867. DOI: 10.1038/s41598-023-50744-7. Cite. Display options. Format. Abstract. Ovarian cancer (OVCA), a prevalent gynecological malignancy, ranks as the fourth most common cancer among women. Mitotic Arrest Deficient 2 Like 2 (MAD2L2), a chromatin-binding protein and a component of DNA polymerase ζ, has been previously identified as an inhibitor of tumor growth in colorectal cancer. However, the roles of MAD2L2 in OVCA, including its expression, impact, and prognostic significance, remain unclear. We employed bioinformatics tools, Cox Regression analysis, and in vitro cell experiments to investigate its biological functions. Our findings reveal that MAD2L2 typically undergoes genomic alterations, such as amplifications and deep deletions. Moreover, we observed an overexpression of MAD2L2 mRNA in OVCA patients, correlating with reduced survival rates, particularly in those with Grade IV tumors. Furthermore, analysis of mRNA biofunctions indicated that MAD2L2 is predominantly localized in the organellar ribosome, engaging mainly in NADH dehydrogenase activity. This was deduced from the results of gene ontology enrichment analysis, which also identified its role as a structural constituent in mitochondrial translation elongation. These findings were corroborated by KEGG pathway analysis, further revealing MAD2L2's involvement in tumor metabolism and the cell death process. Notably, MAD2L2 protein expression showed significant associations with various immune cells, including CD4+T cells, CD8+T cells, B cells, natural killer cells, and Myeloid dendritic cells. Additionally, elevated levels of MAD2L2 were found to enhance cell proliferation and migration in OVCA cells. The upregulation of MAD2L2 also appears to inhibit the ferroptosis process, coinciding with increased mTOR signaling activity in these cells. Our study identifies MAD2L2 as a novel regulator in ovarian tumor progression and offers new insights for treating OVCA. © 2024. The Author(s). PubMed Disclaimer. Conflict of interest statement. The authors declare no competing interests. Figures. Figure 1. The gene expression of MAD2L2… Figure 1. The gene expression of MAD2L2 in pan-cancer and survival time of five common… Figure 2. The clinical feature of MAD2L2… Figure 2. The clinical feature of MAD2L2 in OVCA patients. ( A ) The different… Figure 3. The gene alteration of MAD2L2… Figure 3. The gene alteration of MAD2L2 in OVCA. ( A , B ) The… Figure 4. The gene enrichment analysis of… Figure 4. The gene enrichment analysis of MAD2L2. The enrichment analysis of MAD2L2. ( A… Figure 5. Protein level expression of MAD2L2… Figure 5. Protein level expression of MAD2L2 in single cell analysis and tumor samples. (… Figure 6. Overexpressed MAD2L2 promotes proliferation and… Figure 6. Overexpressed MAD2L2 promotes proliferation and the survival of OVCA cell lines, and overexpressed… Figure 7. Upregulation of MAD2L2 Suppressed Ferroptosis… Figure 7. Upregulation of MAD2L2 Suppressed Ferroptosis Process and Accompanied by mTOR Signaling activity in… See this image and copyright information in PMC. References. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660. - DOI - PubMed. Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J.(Engl.) 2021;134(7):783–791. doi: 10.1097/CM9.0000000000001474. - DOI - PMC - PubMed. Konstantinopoulos PA, Matulonis UA. Clinical and translational advances in ovarian cancer therapy. Nat. Cancer. 2023;4(9):1239–1257. doi: 10.1038/s43018-023-00617-9. - DOI - PubMed. Norppa N, Staff S, Helminen M, et al. Improved survival after implementation of ultra-radical surgery in advanced epithelial ovarian cancer: Results from a tertiary referral center. Gynecol. Oncol. 2022;165(3):478–485. doi: 10.1016/j.ygyno.2022.03.023. - DOI - PubMed. Janos LT, Hye SC, Mark AM, et al. Phase 3, Randomized, Single-Dose, Open-Label Study to Investigate the Safetyand Efficacy of Pafolacianine Sodium Injection (OTL38) for Intraoperative Imaging of Folate Receptor Positive Ovarian Cancer. ASCO; 2021. MeSH terms. Cell Line, Tumor Actions Search in PubMed Search in MeSH Add to Search. Cell Proliferation / genetics Actions Search in PubMed Search in MeSH Add to Search. Female Actions Search in PubMed Search in MeSH Add to Search. Humans Actions Search in PubMed Search in MeSH Add to Search. Mad2 Proteins / genetics Actions Search in PubMed Search in MeSH Add to Search. Mad2 Proteins / metabolism Actions Search in PubMed Search in MeSH Add to Search. Neoplastic Processes Actions Search in PubMed Search in MeSH Add to Search. Ovarian Neoplasms* / pathology Actions Search in PubMed Search in MeSH Add to Search. Proteins Actions Search in PubMed Search in MeSH Add to Search. RNA, Messenger / genetics Actions Search in PubMed Search in MeSH Add to Search. Substances. Proteins Actions Search in PubMed Search in MeSH Add to Search. RNA, Messenger Actions Search in PubMed Search in MeSH Add to Search. MAD2L2 protein, human Actions Search in PubMed Search in MeSH Add to Search. Mad2 Proteins Actions Search in PubMed Search in MeSH Add to Search. Related information. MedGen. Grants and funding. LQ21H160011/Natural Science Foundation of Zhejiang Province. 2021KY990/Medical and Health Plan of Zhejiang. LinkOut - more resources. Full Text Sources Nature Publishing Group. Research Materials NCI CPTC Antibody Characterization Program. Miscellaneous NCI CPTAC Assay Portal.