Psychosocial Stress and MicroRNA Expression Profiles in Myometrial Tissue of Women Undergoing Surgical Treatment for Uterine Fibroids.

Abstract

Uterine leiomyomas (fibroids) are the most common non-cancerous tumors affecting women. Psychosocial stress is associated with fibroid risk and severity. The relationship between psychosocial stress and fibroid pathogenesis may involve alterations in microRNAs (miRNAs) although this has yet to be examined. We investigated associations between two psychosocial stress measures, a composite measure of recent stressful life events and perceived social status, with expression levels of 401 miRNAs in myometrium (n = 20) and fibroids (n = 44; 20 with paired fibroid and myometrium samples) among pre-menopausal women who underwent surgery for fibroid treatment. We used linear regressions to identify psychosocial stressors associated with miRNAs, adjusting for covariates (age, body mass index, race/ethnicity, and oral contraceptive use). The association between psychosocial stressors and miRNAs was considered statistically significant at an FDR p < 0.10 and showed a monotonic response (nominal p-trend < 0.05). In the myometrium, 21 miRNAs were significantly associated with a composite measure of recent stressful events, and two miRNAs were associated with perceived social status. No fibroid miRNAs were associated with either stress measure. Pathway analyses revealed miRNA-mRNA targets were significantly enriched (FDR p < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids, miR-27a-5p and miR-301b were also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with myometrial miRNA expression and, thus, may have a role in the pathogenesis of fibroids from healthy myometrium.