Division of Public Health Sciences Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Department of Radiology, University of Washington, Seattle Cancer Care Alliance, Seattle, Washington, USA.
Epigenetics. 2022 Dec;17(13):2082-2095. doi: 10.1080/15592294.2022.2107841. Epub 2022 Aug 8.
Postmenopausal women with overweight or obesity have an increased risk of developing breast cancer but many of the mechanisms underlying this association remain to be elucidated. MicroRNAs (miRNAs), short non-coding single-stranded RNAs, regulate many physiological processes by controlling post-transcriptional regulation of mRNA. We measured circulating miRNA from 192 overweight/obese postmenopausal women (50-75 years) who were part of a randomized controlled trial, comparing independent and combined effects of a 12-month reduced-calorie weight-loss diet and exercise programme, versus control. RNA was extracted from stored plasma samples, and 23 selected miRNA targets related to aetiology of breast cancer or obesity were measured using NanoString nCounter miRNA Expression assays. Changes from baseline to 12-months between controls and women in the diet/exercise weight loss arms were analysed using generalized estimating equations modification of linear regression, adjusted for confounders. We next examined changes in levels of circulating miRNA by amount of weight loss (0-10% versus ≥10%). Participants randomized to weight-loss interventions had statistically significantly greater reductions in miR-122 (-7.25%), compared to controls (+ 33.5%, P = 0.009), and miR-122 levels were statistically significantly correlated with weight loss (rho = 0.24; P = 0.001) Increasing weight loss was associated with greater reductions in miR-122 vs. controls (-11.7% (≥10% weight loss); +2.0% (0-10% weight loss) +33.5% (controls); P = 0.006), though this was not significant after correction for multiple testing (P = 0.05/23) Our study supports the effect of weight loss on regulation of miRNA.
超重或肥胖的绝经后妇女患乳腺癌的风险增加，但这种关联的许多机制仍有待阐明。 microRNAs（miRNAs）是一种短的非编码单链 RNA，通过控制 mRNA 的转录后调节来调节许多生理过程。我们测量了 192 名超重/肥胖绝经后妇女（50-75 岁）的循环 miRNA，这些妇女是一项随机对照试验的一部分，该试验比较了为期 12 个月的低热量减肥饮食和运动方案对独立和联合的影响，与对照组相比。从储存的血浆样本中提取 RNA，并使用 NanoString nCounter miRNA Expression assays 测量与乳腺癌或肥胖病因相关的 23 个选定 miRNA 靶标。使用广义估计方程修改线性回归，调整混杂因素，分析对照组和饮食/运动减肥组从基线到 12 个月的变化。接下来，我们通过体重减轻量（0-10%与≥10%）检查循环 miRNA 水平的变化。与对照组相比（+33.5%，P=0.009），随机分配到减肥干预组的参与者的 miR-122 水平显著降低（-7.25%），并且 miR-122 水平与体重减轻呈统计学显著相关（rho=0.24；P=0.001）。与对照组相比，体重减轻量越大，miR-122 的降低幅度越大（-11.7%（≥10%体重减轻）；+2.0%（0-10%体重减轻）；+33.5%（对照组）；P=0.006），但在进行多次检验校正后，这种差异无统计学意义（P=0.05/23）。我们的研究支持体重减轻对 miRNA 调节的影响。
