CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer
Abstract MYD88 is an IL-6 primary response gene and, its upregulation of expression has been shown to be a poor prognostic factor in epithelial ovarian cancer (EOC). We investigated the effects of CpG methylation at the proximal promoter/5’UTR and IL-6/SP1/IRF1 signaling on upregulation of MYD88 and...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-81975-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850103036580462592 |
|---|---|
| author | Junyang Li Bingjie Mei Yi Zhu Jianmei Huang Meiying Li Dengfeng Wang Jianming Huang Guonan Zhang |
| author_facet | Junyang Li Bingjie Mei Yi Zhu Jianmei Huang Meiying Li Dengfeng Wang Jianming Huang Guonan Zhang |
| author_sort | Junyang Li |
| collection | DOAJ |
| description | Abstract MYD88 is an IL-6 primary response gene and, its upregulation of expression has been shown to be a poor prognostic factor in epithelial ovarian cancer (EOC). We investigated the effects of CpG methylation at the proximal promoter/5’UTR and IL-6/SP1/IRF1 signaling on upregulation of MYD88 and prognosis in EOC. We assessed CpG methylation at the proximal promoter/5’UTR of MYD88 using bisulfite sequencing/PCR in 103 EOC patients, 28 normal ovarian tissues and two EOC cell lines with differential expression of MYD88 and identified the impact of the level of CpG methylation on MYD88 upregulation by SP1/IRF1 with knockdown or blockade of IL-6. The proximal promoter/5’UTR of MYD88 was significantly hypomethylated in 75 EOC tissues compared to 28 normal ovarian tissues (P < 0.001). CpG hypomethylation was relevant to MYD88 upregulation in 75 EOC cases (R2 = 0.4376; P < 0.001). Of them, 38 cases with m5CpGlow/MYD88high/IL-6high were associated with reduced progression-free/overall survival compared to 37 cases with m5CpGhigh/MYD88low/IL-6low (P < 0.01). Knockdown of IL-6 or blockade with IL-6 receptor McAb attenuated MYD88 upregulation by SP1/IRF1 signaling in EOC cells with MYD88high (P < 0.001). In conclusion, CpG hypomethylation at the proximal promoter/5’UTR contributes to MYD88 upregulation in EOC via IL-6/SP1/IRF1 pathway. |
| format | Article |
| id | doaj-art-8a63932c64664ed7af0ea780262bb85a |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8a63932c64664ed7af0ea780262bb85a2025-08-20T02:39:38ZengNature PortfolioScientific Reports2045-23222024-12-0114111310.1038/s41598-024-81975-xCpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancerJunyang Li0Bingjie Mei1Yi Zhu2Jianmei Huang3Meiying Li4Dengfeng Wang5Jianming Huang6Guonan Zhang7Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaDepartment Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaDepartment Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaDepartment Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaBiochemistry and Molecular Biology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaDepartment Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaBiochemistry and Molecular Biology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaDepartment Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of ChinaAbstract MYD88 is an IL-6 primary response gene and, its upregulation of expression has been shown to be a poor prognostic factor in epithelial ovarian cancer (EOC). We investigated the effects of CpG methylation at the proximal promoter/5’UTR and IL-6/SP1/IRF1 signaling on upregulation of MYD88 and prognosis in EOC. We assessed CpG methylation at the proximal promoter/5’UTR of MYD88 using bisulfite sequencing/PCR in 103 EOC patients, 28 normal ovarian tissues and two EOC cell lines with differential expression of MYD88 and identified the impact of the level of CpG methylation on MYD88 upregulation by SP1/IRF1 with knockdown or blockade of IL-6. The proximal promoter/5’UTR of MYD88 was significantly hypomethylated in 75 EOC tissues compared to 28 normal ovarian tissues (P < 0.001). CpG hypomethylation was relevant to MYD88 upregulation in 75 EOC cases (R2 = 0.4376; P < 0.001). Of them, 38 cases with m5CpGlow/MYD88high/IL-6high were associated with reduced progression-free/overall survival compared to 37 cases with m5CpGhigh/MYD88low/IL-6low (P < 0.01). Knockdown of IL-6 or blockade with IL-6 receptor McAb attenuated MYD88 upregulation by SP1/IRF1 signaling in EOC cells with MYD88high (P < 0.001). In conclusion, CpG hypomethylation at the proximal promoter/5’UTR contributes to MYD88 upregulation in EOC via IL-6/SP1/IRF1 pathway.https://doi.org/10.1038/s41598-024-81975-xEpithelial ovarian cancerMyeloid differentiation factor 88Interleukin-6Specificity protein 1Interferon regulatory factor 1CpG methylation |
| spellingShingle | Junyang Li Bingjie Mei Yi Zhu Jianmei Huang Meiying Li Dengfeng Wang Jianming Huang Guonan Zhang CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer Scientific Reports Epithelial ovarian cancer Myeloid differentiation factor 88 Interleukin-6 Specificity protein 1 Interferon regulatory factor 1 CpG methylation |
| title | CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer |
| title_full | CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer |
| title_fullStr | CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer |
| title_full_unstemmed | CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer |
| title_short | CpG hypomethylation at proximal promoter and 5’UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer |
| title_sort | cpg hypomethylation at proximal promoter and 5 utr along with il6 signaling loop associates with myd88 upregulation in epithelial ovarian cancer |
| topic | Epithelial ovarian cancer Myeloid differentiation factor 88 Interleukin-6 Specificity protein 1 Interferon regulatory factor 1 CpG methylation |
| url | https://doi.org/10.1038/s41598-024-81975-x |
| work_keys_str_mv | AT junyangli cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT bingjiemei cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT yizhu cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT jianmeihuang cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT meiyingli cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT dengfengwang cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT jianminghuang cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer AT guonanzhang cpghypomethylationatproximalpromoterand5utralongwithil6signalingloopassociateswithmyd88upregulationinepithelialovariancancer |