{"title":"HOXD13基因敲低可通过上调MDM2/p53信号通路抑制前列腺癌细胞凋亡。","authors":"Yongliang Ma, Pan Qi, Zongtao Ren, Rui Liu, Shufei Wei, Aili Zhang","doi":"10.1186/s13008-025-00161-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a common leading cause of death worldwide and is recognized as the second most frequently diagnosed cancer in the male population, making it a significant focus of long-term oncological research. The HOXD13 gene, belonging to the HOX gene family, has been associated with various malignancies, including breast and colon cancer, and is associated with prognostic outcomes. However, its specific role in prostate cancer remains to be elucidated.</p><p><strong>Methods: </strong>The correlation of HOXD13 expression in PCa was analyzed by UALCAN database. qRT-PCR and western blot assays were employed to assess the expression levels of HOXD13 in several prostate cancer cell lines. Construct siRNA and overexpression plasmids for HOXD13 and transfect them into cells. Western blot was used to assess the knockdown efficiency of HOXD13 in the cells. The influence of HOXD13 expression on cell proliferation in PC-3 M and C4-2 cells was assessed by EDU staining. The role of HOXD13 in cell migration and invasion of prostate cancer cells was detected by wound healing and transwell assay. Western blot analysis was performed to examine apoptosis-related proteins (C-caspase3, Bax, and Bcl-2) in PC-3 M cells. The co-immunoprecipitation (Co-IP) assay evaluates the interaction between MDM2 and p53.</p><p><strong>Results: </strong>An examination of the data obtained from the UALCAN database reveals that HOXD13 was significantly reduced in prostate cancer tissues and correlated with patient survival. In prostate cancer cell lines, notably PC-3M, HOXD13 expression was markedly reduced. Knockdown of HOXD13 promotes PC-3 M and C4-2 cells proliferation, migration, and invasion. However, the elevated expression of HOXD13 hampers PC-3 M and C4-2 cells proliferation, migration, and invasion. Furthermore, knockdown of HOXD13 in PC-3 M cells resulted in decreased levels of apoptosis markers, including C-caspase-3 and Bax. Co-immunoprecipitation assays demonstrated that HOXD13 depletion enhanced the association between MDM2 and p53.</p><p><strong>Conclusion: </strong>HOXD13 was a critical regulator in the pathogenesis of prostate cancer, modulating the MDM2/p53 signaling pathway to promote apoptosis.</p>","PeriodicalId":49263,"journal":{"name":"Cell Division","volume":"20 1","pages":"18"},"PeriodicalIF":2.2000,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232685/pdf/","citationCount":"0","resultStr":"{\"title\":\"HOXD13 knockdown attenuates apoptosis in prostate cancer via the upregulation of MDM2/p53 signaling.\",\"authors\":\"Yongliang Ma, Pan Qi, Zongtao Ren, Rui Liu, Shufei Wei, Aili Zhang\",\"doi\":\"10.1186/s13008-025-00161-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Prostate cancer (PCa) is a common leading cause of death worldwide and is recognized as the second most frequently diagnosed cancer in the male population, making it a significant focus of long-term oncological research. The HOXD13 gene, belonging to the HOX gene family, has been associated with various malignancies, including breast and colon cancer, and is associated with prognostic outcomes. However, its specific role in prostate cancer remains to be elucidated.</p><p><strong>Methods: </strong>The correlation of HOXD13 expression in PCa was analyzed by UALCAN database. qRT-PCR and western blot assays were employed to assess the expression levels of HOXD13 in several prostate cancer cell lines. Construct siRNA and overexpression plasmids for HOXD13 and transfect them into cells. Western blot was used to assess the knockdown efficiency of HOXD13 in the cells. The influence of HOXD13 expression on cell proliferation in PC-3 M and C4-2 cells was assessed by EDU staining. The role of HOXD13 in cell migration and invasion of prostate cancer cells was detected by wound healing and transwell assay. Western blot analysis was performed to examine apoptosis-related proteins (C-caspase3, Bax, and Bcl-2) in PC-3 M cells. The co-immunoprecipitation (Co-IP) assay evaluates the interaction between MDM2 and p53.</p><p><strong>Results: </strong>An examination of the data obtained from the UALCAN database reveals that HOXD13 was significantly reduced in prostate cancer tissues and correlated with patient survival. In prostate cancer cell lines, notably PC-3M, HOXD13 expression was markedly reduced. Knockdown of HOXD13 promotes PC-3 M and C4-2 cells proliferation, migration, and invasion. However, the elevated expression of HOXD13 hampers PC-3 M and C4-2 cells proliferation, migration, and invasion. Furthermore, knockdown of HOXD13 in PC-3 M cells resulted in decreased levels of apoptosis markers, including C-caspase-3 and Bax. Co-immunoprecipitation assays demonstrated that HOXD13 depletion enhanced the association between MDM2 and p53.</p><p><strong>Conclusion: </strong>HOXD13 was a critical regulator in the pathogenesis of prostate cancer, modulating the MDM2/p53 signaling pathway to promote apoptosis.</p>\",\"PeriodicalId\":49263,\"journal\":{\"name\":\"Cell Division\",\"volume\":\"20 1\",\"pages\":\"18\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-07-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232685/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Division\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13008-025-00161-1\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Division","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13008-025-00161-1","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
HOXD13 knockdown attenuates apoptosis in prostate cancer via the upregulation of MDM2/p53 signaling.
Background: Prostate cancer (PCa) is a common leading cause of death worldwide and is recognized as the second most frequently diagnosed cancer in the male population, making it a significant focus of long-term oncological research. The HOXD13 gene, belonging to the HOX gene family, has been associated with various malignancies, including breast and colon cancer, and is associated with prognostic outcomes. However, its specific role in prostate cancer remains to be elucidated.
Methods: The correlation of HOXD13 expression in PCa was analyzed by UALCAN database. qRT-PCR and western blot assays were employed to assess the expression levels of HOXD13 in several prostate cancer cell lines. Construct siRNA and overexpression plasmids for HOXD13 and transfect them into cells. Western blot was used to assess the knockdown efficiency of HOXD13 in the cells. The influence of HOXD13 expression on cell proliferation in PC-3 M and C4-2 cells was assessed by EDU staining. The role of HOXD13 in cell migration and invasion of prostate cancer cells was detected by wound healing and transwell assay. Western blot analysis was performed to examine apoptosis-related proteins (C-caspase3, Bax, and Bcl-2) in PC-3 M cells. The co-immunoprecipitation (Co-IP) assay evaluates the interaction between MDM2 and p53.
Results: An examination of the data obtained from the UALCAN database reveals that HOXD13 was significantly reduced in prostate cancer tissues and correlated with patient survival. In prostate cancer cell lines, notably PC-3M, HOXD13 expression was markedly reduced. Knockdown of HOXD13 promotes PC-3 M and C4-2 cells proliferation, migration, and invasion. However, the elevated expression of HOXD13 hampers PC-3 M and C4-2 cells proliferation, migration, and invasion. Furthermore, knockdown of HOXD13 in PC-3 M cells resulted in decreased levels of apoptosis markers, including C-caspase-3 and Bax. Co-immunoprecipitation assays demonstrated that HOXD13 depletion enhanced the association between MDM2 and p53.
Conclusion: HOXD13 was a critical regulator in the pathogenesis of prostate cancer, modulating the MDM2/p53 signaling pathway to promote apoptosis.
期刊介绍：
Cell Division is an open access, peer-reviewed journal that encompasses all the molecular aspects of cell cycle control and cancer, cell growth, proliferation, survival, differentiation, signalling, gene transcription, protein synthesis, genome integrity, chromosome stability, centrosome duplication, DNA damage and DNA repair.
Cell Division provides an online forum for the cell-cycle community that aims to publish articles on all exciting aspects of cell-cycle research and to bridge the gap between models of cell cycle regulation, development, and cancer biology. This forum is driven by specialized and timely research articles, reviews and commentaries focused on this fast moving field, providing an invaluable tool for cell-cycle biologists.
Cell Division publishes articles in areas which includes, but not limited to:
DNA replication, cell fate decisions, cell cycle & development
Cell proliferation, mitosis, spindle assembly checkpoint, ubiquitin mediated degradation
DNA damage & repair
Apoptosis & cell death
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