SAT-200 Therapeutic Targeting of Functional MicroRNA Expression by Curcumin in Human Endometrial Stromal Cells

Endometriosis is a chronic gynecological inflammatory disorder in which immune system dysregulation is thought to play a role in its initiation and progression. Current agency-approved hormonal therapies, including synthetic progestins, GnRH-agonists, and danazol are often of limited efficacy and counterproductive to fertility, and cause systemic side effects due to suppression of endogenous steroid hormone production. Our recent publication (PMID: 30259980) suggests that curcumin (diferuloylmethane, CUR), an anti-inflammatory folk medicine in Asian countries, has therapeutic potential to reduce inflammation associated with endometriosis. Therefore, in the current studies we examined the effects of CUR at different doses over a time course in the regulation of proinflammatory and proangiogenic microRNAs (miRNAs) in primary cultures of normal endometrial stromal cells (NESC) and cells derived from eutopic endometrium of endometriosis subjects (EESC). miRNAs are non-coding RNAs that regulate protein translation and have been shown to be involved in the pathogenesis of endometriosis. Using NanoString nCounter-based assays and semi-quantitative RT-PCR we have identified levels of several proinflammatory and proangiogenic miRNAs (including has-miR-196b-5p, has-miR-199a-5p, has-miR-21-5p) that are higher in EESC compared to NESC. EESC and NESC treatment with CUR significantly reduced expression of proinflammatory and proangiogenic miRNAs in a dose- and time-dependent manner. Notably, CUR significantly decreased phosphorylation of the AKT, ERK and prohibitin signaling pathways. These findings demonstrate higher proinflammatory and proangiogenic miRNA production in EESC compared to NESC under basal conditions, and suggest that by suppressing these factors, CUR has the therapeutic potential to reduce inflammation associated with endometriosis. Nothing to Disclose: IC; SB; AD; WX; CN; NS, RNT, WET. Sources of Research Support: This study was supported in part by National Institutes of Health Grants 1SC3 GM113751, U01 HD66439, 1R01HD057235, U54 CA118948, HD41749, S21MD000101 and G12-MD007602. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Grant #C06 RR018386 from NIH/NCRR.