Weight loss reduces circulating micro-RNA related to obesity and breast cancer in postmenopausal women

ABSTRACT

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 a priori 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_trend = 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.

Keywords:

• miRNA
• micro RNA
• randomized controlled trial
• weight loss
• postmenopausal women
• overweight/obesity
• breast cancer

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author (CD) and PI of the parent grant (AMcT), upon reasonable request

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2022.2107841

Additional information

Funding

This work was supported by grants from the National Cancer Institute at the National Institutes of Health (P30 CA015704, R01 CA105204-01A1 and U54-CA116847), and the Breast Cancer Research Foundation (BCRF-16-106, BCRF-17-105, BCRF-18-107 BCRF-19-107).