High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues.
Accumulating data have shown the involvement of microRNAs (miRNAs) in endometriosis pathogenesis. In this study, we used a novel approach to determine the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissues together with eutopic endometria of the same patients. We found five miRNAs specific to epithelial cells--miR-34c, miR-449a, miR-200a, miR-200b and miR-141 showing significantly higher expression in peritoneal endometriotic lesions compared to healthy peritoneal tissues. We also determined the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2 and found that the expression level of E-cadherin was significantly higher in endometriotic lesions compared to healthy tissues. Further evaluation verified that studied miRNAs could be used as diagnostic markers for confirming the presence of endometrial cells in endometriotic lesion biopsy samples. Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic lesion biopsies is largely masked by the surrounding peritoneal tissue, challenging the discovery of an accurate lesion-specific miRNA profile. Taken together, our findings indicate that only particular miRNAs with a significantly higher expression in endometriotic cells can be detected from lesion biopsies, and can serve as diagnostic markers for endometriosis.
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia; Institute of Bio- and Translational Medicine, University of Tartu, Tartu, Estonia.
Merli
M
Saare
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.
Kadri
K
Rekker
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.
Triin
T
Laisk-Podar
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Tartu University Hospital's Women's Clinic, Tartu, Estonia; Elite Clinic, Sangla 63, Tartu, Estonia.
Deniss
D
Sõritsa
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
Anne Mari
AM
Roost
Department of Electrical Engineering (ESAT), STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium; iMinds Medical IT, Leuven, Belgium; Centre for Biology of Integrated Systems, Tallinn University of Technology, Tallinn, Estonia.
Jaak
J
Simm
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Centre for Biology of Integrated Systems, Tallinn University of Technology, Tallinn, Estonia.
Agne
A
Velthut-Meikas
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
Külli
K
Samuel
Institute of Computer Science, University of Tartu, Tartu, Estonia.
Tauno
T
Metsalu
Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia; Tartu University Hospital's Women's Clinic, Tartu, Estonia.
Helle
H
Karro
Elite Clinic, Sangla 63, Tartu, Estonia.
Andrei
A
Sõritsa
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia; Institute of Bio- and Translational Medicine, University of Tartu, Tartu, Estonia.
Andres
A
Salumets
Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia; Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.
Maire
M
Peters
D000328:Adult; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D010537:Peritoneum / Q000473:pathology*; D012016:Reference Values; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; D018398:Homeodomain Proteins; C533895:MIRN141 microRNA, human; C533896:MIRN200 microRNA, human; C522425:MIRN34 microRNA, human; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1