Dye Christian K, Wu Haotian, VanNoy Brianna, Calluori Stephanie, Marfori Cherie Q, Baccarelli Andrea A, Zota Ami R
Department of Environmental Health Sciences, Columbia University.
Ohio State University College of Medicine.
Res Sq. 2023 Sep 21:rs.3.rs-3373251. doi: 10.21203/rs.3.rs-3373251/v1.
Uterine leiomyomas (fibroids) are the most common non-cancerous tumor 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 matched between tissues) from 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, and race/ethnicity). Psychosocial stressors were modeled as ordinal variables and results were considered statistically significant if the overall variable significant was below false discovery threshold (FDR < 0.10) and showed a monotonic dose-response (nominal p-trend < 0.05). In the myometrium, 16 miRNAs were significantly associated with total 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 < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids ( < 0.05), miR-27a-5p was also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with changes in myometrium miRNAs, and thus, plays a role in the pathogenesis of fibroids from healthy myometrium.
子宫平滑肌瘤（纤维瘤）是影响女性的最常见的非癌性肿瘤。心理社会压力与纤维瘤风险及严重程度相关。心理社会压力与纤维瘤发病机制之间的关系可能涉及微小RNA（miRNA）的改变，尽管这一点尚未得到研究。我们调查了两种心理社会压力指标，即近期应激性生活事件和感知社会地位的综合指标，与接受纤维瘤治疗手术的绝经前女性子宫肌层（n = 20）和纤维瘤（n = 44；20对组织配对）中401种miRNA表达水平之间的关联。我们使用线性回归来确定与miRNA相关的心理社会压力源，并对协变量（年龄、体重指数和种族/民族）进行调整。心理社会压力源被建模为有序变量，如果总体变量显著性低于错误发现阈值（FDR < 0.10）且显示单调剂量反应（名义p趋势 < 0.05），则结果被认为具有统计学显著性。在子宫肌层中，16种miRNA与总的应激事件显著相关，两种miRNA与感知社会地位相关。没有纤维瘤miRNA与任何一种压力指标相关。通路分析显示，miRNA - mRNA靶标在与癌症/肿瘤发展相关的通路中显著富集（FDR < 0.05）。在子宫肌层和纤维瘤之间差异表达的74种miRNA中（< 0.05），miR - 27a - 5p也与应激暴露相关。我们的初步分析表明，心理社会压力与子宫肌层miRNA的变化相关，因此，在健康子宫肌层纤维瘤的发病机制中起作用。
