P-342 Altered long non-coding RNA (lncRNA) regulation in endometriosis

Abstract Study question Which Long Non-Coding RNA (lncRNA) are involved in epigenetic regulation in endometriosis? Summary answer The initial analysis of the available transcriptomic datasets enabled the identification of the main lncRNAs involved in the regulation of endometriosis What is known already Endometriosis is a chronic disorder characterised by endometrium-like tissue outside the uterine cavity. It is oestrogen-dependent and commonly presents with symptoms such as chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Its exact etiology has not yet been defined, but there is evidence suggesting the interaction between genetic, hormonal, immunological, and environmental factors. Epigenetic modifications contribute to the pathophysiology of the disease, affecting key biological. Long non-coding RNAs (lncrRNAs) are important epigenetic regulators in various diseases and are implicated in growth and proliferation pathways related to endometriosis. Study design, size, duration Meta-analysis of bulk-RNA-seq datasets from women with endometriosis. Participants/materials, setting, methods Differentially expressed genes (DEGs) were identified by comparing endometrium, ovary, bladder, peritoneum and intestine samples with their respective controls. Genes with log2-fold ≥ 1 or ≤ -1 in bulk RNA-seq, with adjusted p < 0.05, were considered differentially expressed. Genes common to all sets were included in the meta-analysis. Functional analysis was carried out using the Enrichr and String tools to explore the interactions between lncRNAs and coding genes. Main results and the role of chance In the Bulk RNA-seq datasets, 11 consensus lncRNA genes were identified, including LINC02984, GATA6-AS1, LINCPINT, CASC15, PCBP1-AS1, FAM13A-AS1, TMEM161B-DT and MALAT1, all of which are up-regulated. Interaction analysis using the String tool revealed that these lncRNAs are associated with activation of the complement system and coagulation pathways. Among them, MALAT1 is the best known for regulating genes involved in cell migration, cell cycle regulation and its up-regulation related to cell proliferation. In addition, the lncRNAs MIR29B2CHG, LINC02884 and LETR1 showed reduced regulation. These lncRNAs were associated with the modulation of genes involved in apoptosis, inflammatory response, cell signalling and regulation of the oestrogen receptor (ERα). These findings were corroborated by the results of the functional enrichment analysis, which indicated that the positively regulated genes are enriched in pathways related to activation of the complement system, regulation of TGF-β signalling, inflammatory processes and cell adhesion molecules. In contrast, the negatively regulated genes were associated with double-stranded DNA repair and cellular senescence pathways. Limitations, reasons for caution Inadequate normalisation can generate biases, while low expression transcripts can go unnoticed. To overcome these limitations, techniques such as single-cell RNA-Seq (scRNA-seq) is an alternative that allows for a more precise analysis of cellular heterogeneity and the underlying biological mechanisms. Wider implications of the findings lncRNAs have potential as biomarkers for early detection and therapeutic targets for intervention, and hold promise for improving diagnostic and treatment strategies. Further research into lncRNA-mediated regulatory networks may provide new insights into disease progression, facilitating the development of personalised medicine approaches. Trial registration number No