Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets
Abstract Polycystic ovary syndrome (PCOS) is a known risk factor for uterine endometrial cancer (UCEC), but its underlying mechanisms remain unclear. MicroRNAs (miRNAs) could provide insights into these mechanisms and reveal potential therapeutic targets. Differential miRNA expression was analyzed i...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-02-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-01861-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823862006681174016 |
|---|---|
| author | Xuedan Lai Ling Wu Peihong Lin Lijiao You Jianwen Ye |
| author_facet | Xuedan Lai Ling Wu Peihong Lin Lijiao You Jianwen Ye |
| author_sort | Xuedan Lai |
| collection | DOAJ |
| description | Abstract Polycystic ovary syndrome (PCOS) is a known risk factor for uterine endometrial cancer (UCEC), but its underlying mechanisms remain unclear. MicroRNAs (miRNAs) could provide insights into these mechanisms and reveal potential therapeutic targets. Differential miRNA expression was analyzed in plasma exosomes from 15 PCOS and 15 control samples. Survival analysis assessed the prognostic value of these miRNAs in UCEC. MiRNA-target gene interaction networks and gene co-expression analyses were used to explore molecular mechanisms. Validation was performed using experimental data from Ishikawa cells treated with six candidate drugs. Among the 15 differentially expressed miRNAs, 12 were up-regulated and 3 were down-regulated in PCOS. Twelve of these miRNAs were associated with UCEC overall survival, with miR-142, miR-424, and miR-331 acting as protective factors, while the remaining 9 miRNAs were identified as risk factors. MiRNA-target network highlighted key genes such as PHF8, LCOR, SFT2D3, E2F1, and ESR1, which were found to be prognostic for patient survival. Further gene expression and co-expression analyses based on miR-424 and miR-330 expression revealed significant alterations in gene expression and cellular processes related to UCEC. Two-sample Mendelian randomization analysis identified potential causal relationships between AURKA gene expression and PCOS or UCEC. Testosterone and estradiol might have adverse roles in UCEC, while drugs like troglitazone, valproic acid, retinoic acid, and progesterone demonstrated various effects on gene expression and cellular processes. Our findings suggest that aberrant miRNA expression, particularly miR-330 and miR-424, may play crucial roles in UCEC progression. The identified miRNAs and candidate drugs may serve as potential therapeutic targets for UCEC, but further research is required to validate and explore their clinical applications. |
| format | Article |
| id | doaj-art-d9e975a3749c48a5be064acb6645d3bd |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-d9e975a3749c48a5be064acb6645d3bd2025-02-09T12:43:20ZengSpringerDiscover Oncology2730-60112025-02-0116111410.1007/s12672-025-01861-4Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targetsXuedan Lai0Ling Wu1Peihong Lin2Lijiao You3Jianwen Ye4Department of Gynaecology, Fuzhou First Hospital Affiliated to Fujian Medical UniversityDepartment of Gynaecology, Fuzhou First Hospital Affiliated to Fujian Medical UniversityDepartment of Gynaecology, Fuzhou First Hospital Affiliated to Fujian Medical UniversityDepartment of Gynaecology, Fuzhou First Hospital Affiliated to Fujian Medical UniversityDepartment of Gynaecology, Fuzhou First Hospital Affiliated to Fujian Medical UniversityAbstract Polycystic ovary syndrome (PCOS) is a known risk factor for uterine endometrial cancer (UCEC), but its underlying mechanisms remain unclear. MicroRNAs (miRNAs) could provide insights into these mechanisms and reveal potential therapeutic targets. Differential miRNA expression was analyzed in plasma exosomes from 15 PCOS and 15 control samples. Survival analysis assessed the prognostic value of these miRNAs in UCEC. MiRNA-target gene interaction networks and gene co-expression analyses were used to explore molecular mechanisms. Validation was performed using experimental data from Ishikawa cells treated with six candidate drugs. Among the 15 differentially expressed miRNAs, 12 were up-regulated and 3 were down-regulated in PCOS. Twelve of these miRNAs were associated with UCEC overall survival, with miR-142, miR-424, and miR-331 acting as protective factors, while the remaining 9 miRNAs were identified as risk factors. MiRNA-target network highlighted key genes such as PHF8, LCOR, SFT2D3, E2F1, and ESR1, which were found to be prognostic for patient survival. Further gene expression and co-expression analyses based on miR-424 and miR-330 expression revealed significant alterations in gene expression and cellular processes related to UCEC. Two-sample Mendelian randomization analysis identified potential causal relationships between AURKA gene expression and PCOS or UCEC. Testosterone and estradiol might have adverse roles in UCEC, while drugs like troglitazone, valproic acid, retinoic acid, and progesterone demonstrated various effects on gene expression and cellular processes. Our findings suggest that aberrant miRNA expression, particularly miR-330 and miR-424, may play crucial roles in UCEC progression. The identified miRNAs and candidate drugs may serve as potential therapeutic targets for UCEC, but further research is required to validate and explore their clinical applications.https://doi.org/10.1007/s12672-025-01861-4miRNAsEndometrial cancerPolycystic ovary syndrome (PCOS)Integrative analysisGene expression |
| spellingShingle | Xuedan Lai Ling Wu Peihong Lin Lijiao You Jianwen Ye Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets Discover Oncology miRNAs Endometrial cancer Polycystic ovary syndrome (PCOS) Integrative analysis Gene expression |
| title | Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets |
| title_full | Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets |
| title_fullStr | Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets |
| title_full_unstemmed | Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets |
| title_short | Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets |
| title_sort | plasma mirnas in polycystic ovary syndrome drive endometrial cancer progression insights into molecular pathways and therapeutic targets |
| topic | miRNAs Endometrial cancer Polycystic ovary syndrome (PCOS) Integrative analysis Gene expression |
| url | https://doi.org/10.1007/s12672-025-01861-4 |
| work_keys_str_mv | AT xuedanlai plasmamirnasinpolycysticovarysyndromedriveendometrialcancerprogressioninsightsintomolecularpathwaysandtherapeutictargets AT lingwu plasmamirnasinpolycysticovarysyndromedriveendometrialcancerprogressioninsightsintomolecularpathwaysandtherapeutictargets AT peihonglin plasmamirnasinpolycysticovarysyndromedriveendometrialcancerprogressioninsightsintomolecularpathwaysandtherapeutictargets AT lijiaoyou plasmamirnasinpolycysticovarysyndromedriveendometrialcancerprogressioninsightsintomolecularpathwaysandtherapeutictargets AT jianwenye plasmamirnasinpolycysticovarysyndromedriveendometrialcancerprogressioninsightsintomolecularpathwaysandtherapeutictargets |