Exosomal Long Noncoding RNA-NONHAT076754 Faciliates Endometriosis Invasion and Predicts Endometriosis Recurrence

Abstract

Study Objective Exosome-mediated transfer of long noncoding RNAs (lncRNAs) to influence recipient cells is emerging as a novel mechanism for disease progression. NONHAT076754 is a newly identified metastasis-related lncRNA involved in cancer. Since endometriosis exhibits malignancy-like prometastasis behaviour similar to those observed in cancer, we aimed to investigate whether NONHAT076754 is involved in endometriosis and, if so, whether the exosome-mediated transfer of NONHAT076754 contributes to endometriosis migration/invasion. Additionally, we aimed to investigate the clinical value of serum exosomal NONHAT076754 in endometriosis. Design A molecular and clinical retrospective study. Setting Obstetrics and Gynecology Hospital of Fudan University. Patients or Participants Ninety two patients with ovarian endometriotic cysts recruited from 2014 to 2016. Interventions N/A. Measurements and Main Results The distribution and expression of NONHAT076754 in ectopic, eutopic and normal endometria was evaluated using fluorescence in situ hybridization and real-time polymerase chain reaction. Isolation, characterization, labeling and tracking of exosomes were performed. Migration/invasion assays were conducted. We found that NONHAT076754 was highly expressed in ectopic endometrial stromal tissues than in the paired eutopic and normal endometria. In vitro, using NONHAT076754-high-expression ectopic endometrial stromal cells (Ec-ESCs) as exosome-generating cells and NONHAT076754-low-expression eutopic endometrial stromal cells (Eu-ESCs) as recipient cells, we observed that the PKH67-labeled Ec-ESCs derived exosomes were effectively internalized by recipient Eu-ESCs. Exosome-shuttled NONHAT076754 was transferred from Ec-ESCs to Eu-ESCs which in turn elicited the migratory/invasive ability of Eu-ESCs partially by regulating ZO-1, E-cadherin and N-cadherin, eventually facilitating endometriosis migration/invasion. Notably, elevated serum exosomal NONHAT076754 expression was associated with clinical stages and recurrence of endometriosis (P Conclusion Our study suggests a novel mechanism for the malignancy-like prometastasis behaviour of endometriosis from the perspective of the “exosomal transfer of lncRNAs” and highlights the potential of serum exosomal NONHAT076754 as a biomarker for endometriosis recurrence.