miR-193b-5p and miR-374b-5p Are Aberrantly Expressed in Endometriosis and Suppress Endometrial Cell Migration In Vitro
Caroline Frisendahl,
Yiqun Tang,
Nageswara Rao Boggavarapu,
Maire Peters,
Parameswaran Grace Lalitkumar,
Terhi T. Piltonen,
Riikka K. Arffman,
Andres Salumets,
Martin Götte,
Eberhard Korsching,
Kristina Gemzell-Danielsson
Affiliations
Caroline Frisendahl
WHO Collaborating Centre, Division of Neonatology, Obstetrics, Gynecology, and Reproductive Health, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, SE 17176 Stockholm, Sweden
Yiqun Tang
WHO Collaborating Centre, Division of Neonatology, Obstetrics, Gynecology, and Reproductive Health, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, SE 17176 Stockholm, Sweden
Nageswara Rao Boggavarapu
WHO Collaborating Centre, Division of Neonatology, Obstetrics, Gynecology, and Reproductive Health, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, SE 17176 Stockholm, Sweden
Maire Peters
Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia
Parameswaran Grace Lalitkumar
WHO Collaborating Centre, Division of Neonatology, Obstetrics, Gynecology, and Reproductive Health, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, SE 17176 Stockholm, Sweden
Terhi T. Piltonen
Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Medical Research Centre, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
Riikka K. Arffman
Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Medical Research Centre, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
Andres Salumets
Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia
Martin Götte
Department of Gynecology and Obstetrics, University Hospital of Münster, University of Münster, 48149 Münster, Germany
Eberhard Korsching
Institute of Bioinformatics, University Hospital of Münster, University of Münster, 48149 Münster, Germany
Kristina Gemzell-Danielsson
WHO Collaborating Centre, Division of Neonatology, Obstetrics, Gynecology, and Reproductive Health, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, SE 17176 Stockholm, Sweden
(1) Background: Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. This study aimed to identify differentially expressed miRNAs in endometriosis and study their functions in the disease. (2) Methods: Endometrial tissue was collected from women with endometriosis (n = 15) and non-endometriosis controls (n = 17). Dysregulated miRNAs were identified through small RNA-sequencing, and their biological significance was explored by target gene prediction and pathway analysis. Selected miRNAs were examined in paired ectopic endometriomas and eutopic endometrium (n = 10) using qRT-PCR. Their roles in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing on transfected cells and the endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in the eutopic endometrium of women with endometriosis compared to endometrial tissue from women without endometriosis. Pathway analysis indicated enrichment in cell migration and proliferation-associated pathways. Further ex vivo studies of miR-193b-5p and miR-374b-5p showed that both miRNAs were upregulated in endometrioma. Overexpression of these two miRNAs in vitro inhibited cell migration, and mRNA sequencing revealed several migration-related genes that are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration.
