title: MicroRNA-regulated pathways associated with endometriosis.
abstract: Endometriosis is a prevalent gynecological disease characterized by growth of endometriotic tissue outside the uterine cavity. MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development. We assessed miRNA expression by microarray analysis in paired ectopic and eutopic endometrial tissues and identified 14 up-regulated (miR-145, miR-143, miR-99a, miR-99b, miR-126, miR-100, miR-125b, miR-150, miR-125a, miR-223, miR-194, miR-365, miR-29c and miR-1) and eight down-regulated (miR-200a, miR-141, miR-200b, miR-142-3p, miR-424, miR-34c, miR-20a and miR-196b) miRNAs. The differential expression of six miRNAs was confirmed by quantitative RT-PCR. An in silico analysis identified 3851 mRNA transcripts as putative targets of the 22 miRNAs. Of these predicted targets, 673 were also differentially expressed in ectopic vs. eutopic endometrial tissue, as determined by microarray. Functional analysis suggested that the 673 miRNA targets constitute molecular pathways previously associated with endometriosis, including c-Jun, CREB-binding protein, protein kinase B (Akt), and cyclin D1 (CCND1) signaling. These pathways appeared to be regulated both transcriptionally as well as by miRNAs at posttranscriptional level. These data are a rich and novel resource for endometriosis and miRNA research and suggest that the 22 miRNAs and their cognate mRNA target sequences constitute pathways that promote endometriosis. Accordingly, miRNAs are potential therapeutic targets for treating this disease.
authors.affiliation: Research Centre for Reproductive Health, University of Adelaide, South Australia 5005, Australia. maria.teague@adelaide.edu.au
authors.forename: E Maria C
authors.initials: EM
authors.lastname: Ohlsson Teague
authors.forename: Kylie H
authors.initials: KH
authors.lastname: Van der Hoek
authors.forename: Mark B
authors.initials: MB
authors.lastname: Van der Hoek
authors.forename: Naomi
authors.initials: N
authors.lastname: Perry
authors.forename: Prabhath
authors.initials: P
authors.lastname: Wagaarachchi
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Robertson
authors.forename: Cristin G
authors.initials: CG
authors.lastname: Print
authors.forename: Louise M
authors.initials: LM
authors.lastname: Hull
mesh_terms: D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D048031:JNK Mitogen-Activated Protein Kinases