SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer
Abstract Background Ovarian cancer (OC) is the most lethal gynecologic malignant tumour. The mechanism promoting OC initiation and progression remains unclear. SET domain bifurcated histone lysine methyltransferase 1(SETDB1) acts as an oncogene in a variety of tumours. This study aims to explore the...
| Main Authors: | , , , , |
|---|---|
| 格式: | 文件 |
| 语言: | English |
| 出版: |
BMC
2024-02-01
|
| 丛编: | Journal of Ovarian Research |
| 主题: | |
| 在线阅读: | https://doi.org/10.1186/s13048-024-01358-8 |
| _version_ | 1827326528386498560 |
|---|---|
| author | Hongjuan Yang Lei Sui Cuicui Cai Huijun Chu Yuchao Diao |
| author_facet | Hongjuan Yang Lei Sui Cuicui Cai Huijun Chu Yuchao Diao |
| author_sort | Hongjuan Yang |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer (OC) is the most lethal gynecologic malignant tumour. The mechanism promoting OC initiation and progression remains unclear. SET domain bifurcated histone lysine methyltransferase 1(SETDB1) acts as an oncogene in a variety of tumours. This study aims to explore the role of SETDB1 in OC. Methods GEO, TCGA, CSIOVDB and CPTAC databases jointly analysed SETDB1 mRNA and protein expression. Effect of SETDB1 expression on the clinical prognosis of OC patients was analysed through online Kaplan‒Meier plotter and CSIOVDB database. Then, the effect of SETDB1 in OC cells progression and mobility was examined using MTT, EdU, colony formation and transwell assay. Additionally, Cistrome DB database was used to visualize the binding of SETDB1 protein and splicing factor 3b subunit 4 (SF3B4) promoter, and dual-luciferase reporter gene assay was performed to confirm the interaction. Finally, bioinformatics analysis was employed to reveal the relationship between SETDB1 and the microenvironment of OC. Results In the present study, we found that SETDB1 was obviously upregulated in OC and its overexpression predicted poor prognosis of OC patients. Then, we verified that SETDB1 promoted the progression and motility of OC cells in vitro. Knockdown of SETDB1 had the opposite effect. Further research showed that SETDB1 acted as a transcription factor to activate SF3B4 expression. SF3B4 knockdown impaired the effect of SETDB1 to promote the proliferative capacity and motility of OC cells. Finally, the results of bioinformatics analysis confirmed that SETDB1 regulated the immune microenvironment of ovarian cancer. Conclusion SETDB1 promoted ovarian cancer progression by upregulating the expression of SF3B4 and inhibiting the tumour immunity. SETDB1 may be a promising prognostic and therapeutic marker for OC. |
| first_indexed | 2024-03-07T14:46:52Z |
| format | Article |
| id | doaj.art-95df38d8f83046e6a035bf5c92ae295e |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-03-07T14:46:52Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-95df38d8f83046e6a035bf5c92ae295e2024-03-05T19:58:10ZengBMCJournal of Ovarian Research1757-22152024-02-0117111410.1186/s13048-024-01358-8SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancerHongjuan Yang0Lei Sui1Cuicui Cai2Huijun Chu3Yuchao Diao4Department of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao UniversityDepartment of Gynecological Oncology, Qingdao Central Hospital, University of Health and Rehabilitation SciencesDepartment of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao UniversityDepartment of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao UniversityDepartment of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao UniversityAbstract Background Ovarian cancer (OC) is the most lethal gynecologic malignant tumour. The mechanism promoting OC initiation and progression remains unclear. SET domain bifurcated histone lysine methyltransferase 1(SETDB1) acts as an oncogene in a variety of tumours. This study aims to explore the role of SETDB1 in OC. Methods GEO, TCGA, CSIOVDB and CPTAC databases jointly analysed SETDB1 mRNA and protein expression. Effect of SETDB1 expression on the clinical prognosis of OC patients was analysed through online Kaplan‒Meier plotter and CSIOVDB database. Then, the effect of SETDB1 in OC cells progression and mobility was examined using MTT, EdU, colony formation and transwell assay. Additionally, Cistrome DB database was used to visualize the binding of SETDB1 protein and splicing factor 3b subunit 4 (SF3B4) promoter, and dual-luciferase reporter gene assay was performed to confirm the interaction. Finally, bioinformatics analysis was employed to reveal the relationship between SETDB1 and the microenvironment of OC. Results In the present study, we found that SETDB1 was obviously upregulated in OC and its overexpression predicted poor prognosis of OC patients. Then, we verified that SETDB1 promoted the progression and motility of OC cells in vitro. Knockdown of SETDB1 had the opposite effect. Further research showed that SETDB1 acted as a transcription factor to activate SF3B4 expression. SF3B4 knockdown impaired the effect of SETDB1 to promote the proliferative capacity and motility of OC cells. Finally, the results of bioinformatics analysis confirmed that SETDB1 regulated the immune microenvironment of ovarian cancer. Conclusion SETDB1 promoted ovarian cancer progression by upregulating the expression of SF3B4 and inhibiting the tumour immunity. SETDB1 may be a promising prognostic and therapeutic marker for OC.https://doi.org/10.1186/s13048-024-01358-8SETDB1Transcription factorSF3B4Ovarian cancerTumour immunity |
| spellingShingle | Hongjuan Yang Lei Sui Cuicui Cai Huijun Chu Yuchao Diao SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer Journal of Ovarian Research SETDB1 Transcription factor SF3B4 Ovarian cancer Tumour immunity |
| title | SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer |
| title_full | SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer |
| title_fullStr | SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer |
| title_full_unstemmed | SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer |
| title_short | SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer |
| title_sort | setdb1 promotes progression through upregulation of sf3b4 expression and regulates the immunity in ovarian cancer |
| topic | SETDB1 Transcription factor SF3B4 Ovarian cancer Tumour immunity |
| url | https://doi.org/10.1186/s13048-024-01358-8 |
| work_keys_str_mv | AT hongjuanyang setdb1promotesprogressionthroughupregulationofsf3b4expressionandregulatestheimmunityinovariancancer AT leisui setdb1promotesprogressionthroughupregulationofsf3b4expressionandregulatestheimmunityinovariancancer AT cuicuicai setdb1promotesprogressionthroughupregulationofsf3b4expressionandregulatestheimmunityinovariancancer AT huijunchu setdb1promotesprogressionthroughupregulationofsf3b4expressionandregulatestheimmunityinovariancancer AT yuchaodiao setdb1promotesprogressionthroughupregulationofsf3b4expressionandregulatestheimmunityinovariancancer |