Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer
Growing evidence suggests an association between Mycoplasma infections and the development and progression of prostate cancer (PCa). In this study, we report that chronic and persistent M. hyorhinis infection induced robust TNF-α secretion from PCa cells. TNF-α secreted from M. hyorhinis-infected PC...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023078635 |
| _version_ | 1797646511166717952 |
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| author | Jin Koo Kim Insoon Chang Younghun Jung Zach Kaplan Elliott E. Hill Russell S. Taichman Paul H. Krebsbach |
| author_facet | Jin Koo Kim Insoon Chang Younghun Jung Zach Kaplan Elliott E. Hill Russell S. Taichman Paul H. Krebsbach |
| author_sort | Jin Koo Kim |
| collection | DOAJ |
| description | Growing evidence suggests an association between Mycoplasma infections and the development and progression of prostate cancer (PCa). In this study, we report that chronic and persistent M. hyorhinis infection induced robust TNF-α secretion from PCa cells. TNF-α secreted from M. hyorhinis-infected PCa cells subsequently led to activation of the NF-κB pathway. Chronic M. hyorhinis infection induced gene expression of pro-inflammatory cytokines and chemokines in a NF-κB-dependent manner and promoted cell proliferation, migration, and invasion in PCa cells. The elimination of M. hyorhinis in PCa cells significantly blocked TNF-α secretion, gene expression of cytokines and chemokines, migration, and invasion in PCa cells, suggesting M. hyorhinis-induced TNF-α plays an important role to promote malignant transformation of PCa. Furthermore, second mitochondria-derived activator of caspases (SMAC) mimetics potentiated caspase activation and cell death in M. hyorhinis-infected PCa by antagonizing inhibitor of apoptosis proteins (IAPs) activity. Tissue microarray analysis indicated that TNF-α is co-expressed in M. hyorhinis-infected human patient tissues. Findings from this study advance our understanding of the mycoplasma-oncogenesis process and suggest the potential for new approaches for preventions, diagnosis, and therapeutic approaches against prostate cancers. |
| first_indexed | 2024-03-11T15:02:41Z |
| format | Article |
| id | doaj.art-4f4e06b48a8f41b6bd2e90617bc026f1 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T15:02:41Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-4f4e06b48a8f41b6bd2e90617bc026f12023-10-30T06:06:55ZengElsevierHeliyon2405-84402023-10-01910e20655Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancerJin Koo Kim0Insoon Chang1Younghun Jung2Zach Kaplan3Elliott E. Hill4Russell S. Taichman5Paul H. Krebsbach6Division of Oral and Systemic Health Sciences, University of California, Los Angeles School of Dentistry, Los Angeles, CA, USASection of Endodontics, University of California, Los Angeles School of Dentistry, Los Angeles, CA, USADepartment of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USADepartment of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USADepartment of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USADepartment of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Department of Periodontics, University of Alabama at Birmingham, Birmingham, AL, USADivision of Oral and Systemic Health Sciences, University of California, Los Angeles School of Dentistry, Los Angeles, CA, USA; Corresponding author. University of California, Los Angeles School of Dentistry, Los Angeles, CA, 90095, USA.Growing evidence suggests an association between Mycoplasma infections and the development and progression of prostate cancer (PCa). In this study, we report that chronic and persistent M. hyorhinis infection induced robust TNF-α secretion from PCa cells. TNF-α secreted from M. hyorhinis-infected PCa cells subsequently led to activation of the NF-κB pathway. Chronic M. hyorhinis infection induced gene expression of pro-inflammatory cytokines and chemokines in a NF-κB-dependent manner and promoted cell proliferation, migration, and invasion in PCa cells. The elimination of M. hyorhinis in PCa cells significantly blocked TNF-α secretion, gene expression of cytokines and chemokines, migration, and invasion in PCa cells, suggesting M. hyorhinis-induced TNF-α plays an important role to promote malignant transformation of PCa. Furthermore, second mitochondria-derived activator of caspases (SMAC) mimetics potentiated caspase activation and cell death in M. hyorhinis-infected PCa by antagonizing inhibitor of apoptosis proteins (IAPs) activity. Tissue microarray analysis indicated that TNF-α is co-expressed in M. hyorhinis-infected human patient tissues. Findings from this study advance our understanding of the mycoplasma-oncogenesis process and suggest the potential for new approaches for preventions, diagnosis, and therapeutic approaches against prostate cancers.http://www.sciencedirect.com/science/article/pii/S2405844023078635Mycoplasma hyorhinisProstate cancerTNF-αNF-κBSMAC mimeticAZD5582 |
| spellingShingle | Jin Koo Kim Insoon Chang Younghun Jung Zach Kaplan Elliott E. Hill Russell S. Taichman Paul H. Krebsbach Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer Heliyon Mycoplasma hyorhinis Prostate cancer TNF-α NF-κB SMAC mimetic AZD5582 |
| title | Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer |
| title_full | Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer |
| title_fullStr | Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer |
| title_full_unstemmed | Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer |
| title_short | Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer |
| title_sort | mycoplasma hyorhinis infection promotes tnf α signaling and smac mimetic mediated apoptosis in human prostate cancer |
| topic | Mycoplasma hyorhinis Prostate cancer TNF-α NF-κB SMAC mimetic AZD5582 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023078635 |
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