How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development

Yachida, Nozomi; Yoshihara, Kosuke; Yamaguchi, Manako; Suda, Kazuaki; Tamura, Ryo; Enomoto, Takayuki

doi:10.3390/cancers13061439

Cited by 28 publications

(29 citation statements)

References 85 publications

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“…EMs can be anatomically divided into three sub-groups: superficial peritoneal endometriosis, deeply infiltrating endometriosis, and ovarian endometriosis (O-EMs) [ 2 ]. Notably, O-EMs is accompanied by an elevated risk of ovarian cancer [ 3 ], impaired ovarian reserve, and sterility [ 4 ], as well as the failure of in vitro fertilization [ 5 ]. EMs, as a benign disease, present similar biological characteristics with cancers like invasive and migratory properties, development of local and distant foci, and resistance to apoptosis [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

et al. 2022

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Endometriosis (EMs) is a benign gynecological disorder showing some tumor-like migratory and invasive phenotypes. This study intended to investigate the role of microRNA-30c (miR-30c) in EMs, which is involved with B-cell lymphoma 9 (BCL9), an activator of the Wnt/β-catenin signaling pathway. EMs specimens were clinically collected for determination of miR-30c and BCL9 expression. Exosomes were isolated from endometrial epithelial cells (EECs), and the uptake of exosomes by ectopic EECs (ecto-EECs) was characterized using fluorescence staining and confocal microscopy. The binding of miR-30c to BCL9 was validated by dual-luciferase reporter assay. Artificial modulation (up- and down-regulation) of the miR-30c/BCL9/Wnt/CD44 regulatory cascade was performed to evaluate its effect on ecto-EEC invasion and migration, as detected by Transwell and wound healing assays. A mouse model of EMs was further established for in vivo substantiation. Reduced miR-30c expression and elevated BCL9 expression was revealed in EMs ectopic tissues and ecto-EECs. Normal EECs-derived exosomes delivered miR-30c to ecto-EECs to suppress their invasive and migratory potentials. Then, miR-30c was observed to inhibit biological behaviors of ecto-EECs by targeting BCL9, and the miR-30c-induced inhibitory effect was reversed by BCL9 overexpression. Further, miR-30c diminished the invasion and migration of ecto-EECs by blocking the BCL9/Wnt/CD44 axis. Moreover, miR-30c-loaded exosomes attenuated the metastasis of ecto-EEC ectopic nodules. miR-30c delivered by EECs-derived exosomes repressed BCL9 expression to block the Wnt/β-catenin signaling pathway, thus attenuating the tumor-like behaviors of ecto-EECs in EMs.

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Section: Introductionmentioning

confidence: 99%

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

et al. 2022

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“…The association between endometriosis and ovarian cancer, especially in clear cell carcinoma or endometrioid carcinoma, led to an interest in the role of somatic mutations in genes implicated in ovarian cancer [ 86 , 87 ]. With regard to cancer-associated gene mutations in endometriosis, KRAS , ARID1A , PIK3CA, and PPP2R1A are frequently noted [ 88 , 89 ].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…The impact of these mutations on the development of endometriosis is complex and highlights the need for further evaluation. Moreover, while the association between endometriosis and ovarian cancer has already been examined in numerous studies [ 88 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ], the effect of these mutations on the prevalence of PP has not been reported. Further studies are warranted to examine the effect of these mutations on the prevalence of PP.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Placenta Previa Complicated with Endometriosis: Contemporary Clinical Management, Molecular Mechanisms, and Future Research Opportunities

et al. 2021

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Endometriosis is a common gynecological disease characterized by chronic inflammation, with an estimated prevalence of approximately 5–15% in reproductive-aged women. This study aimed to assess the relationship between placenta previa (PP) and endometriosis. We performed a systematic review of the literature until 30 June 2021, and 24 studies met the inclusion criteria. Using an adjusted pooled analysis, we found that women with endometriosis had a significantly increased rate of PP (adjusted odds ratio (OR) 3.17, 95% confidence interval (CI) 2.58–3.89) compared to those without endometriosis. In an unadjusted analysis, severe endometriosis was associated with an increased prevalence of PP (OR 11.86, 95% CI 4.32–32.57), whereas non-severe endometriosis was not (OR 2.16, 95% CI 0.95–4.89). Notably, one study showed that PP with endometriosis was associated with increased intraoperative bleeding (1.515 mL versus 870 mL, p < 0.01) compared to those without endometriosis. Unfortunately, no studies assessed the molecular mechanisms underlying PP in patients with endometriosis. Our findings suggest that there is a strong association between endometriosis and a higher incidence of PP, as well as poor surgical outcomes during cesarean delivery. Therefore, the development of novel therapeutic agents or methods is warranted to prevent PP in women with endometriosis.

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“…Several studies have shown that endometriosis is one of the risk factors for ovarian cancer [ 8 ], and a proportion of ovarian cancers have been shown to originate from 0.5 to 1% of cases of ovarian endometriosis [ 9 , 10 ]. Ovarian endometriosis may present a risk for ovarian malignant lesions according to gene expression and miRNA alterations [ 11 , 12 ], and is always managed with the prevention of carcinogenesis [ 13 ]. Immunity and inflammation are thought to be strongly associated with carcinogenicity [ 14 , 15 ]; however, no studies have shown how long ovarian cancer takes to develop from ovarian endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Gao

2021

Annals of Medicine

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Aim Endometriosis is one of the most common reproductive system diseases, but the mechanisms of disease progression are still unclear. Due to its high recurrence rate, searching for potential therapeutic biomarkers involved in the pathogenesis of endometriosis is an urgent issue. Methods Due to the similarities between endometriosis and ovarian cancer, four endometriosis datasets and one ovarian cancer dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein–protein interaction (PPI) analyses. Then, we validated gene expression and performed survival analysis with ovarian serous cystadenocarcinoma (OV) datasets in TCGA/GTEx database, and searched for potential drugs in the Drug-Gene Interaction Database. Finally, we explored the miRNAs of key genes to find biomarkers associated with the recurrence of endometriosis. Results In total, 104 DEGs were identified in the endometriosis datasets, and the main enriched GO functions included cell adhesion, extracellular exosome and actin binding. Fifty DEGs were identified between endometriosis and ovarian cancer datasets including 11 consistently regulated genes, and nine DEGs with significant expression in TCGA/GTEx. Only IGHM had both significant expression and an association with survival, three module DEGs and two significantly expressed DEGs had drug associations, and 10 DEGs had druggability. Conclusions ITGA7 , ITGBL1 and SORBS1 may help us understand the invasive nature of endometriosis, and IGHM might be related to recurrence; moreover, these genes all may be potential therapeutic targets. KEY MESSAGE This manuscript used a bioinformatics approach to find target genes for the treatment of endometriosis. This manuscript used a new approach to find target genes by drawing on common characteristics between ovarian cancer and endometriosis. We screened relevant therapeutic agents for target genes in the drug database, and performed histological validation of target genes with both expression and survival analysis difference in cancer databases.

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How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development

Cited by 28 publications

References 85 publications

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

Placenta Previa Complicated with Endometriosis: Contemporary Clinical Management, Molecular Mechanisms, and Future Research Opportunities

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

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