Differential Expression of Small Non-Coding RNAs in Uterine Leiomyomas

We performed next-generation sequencing (NGS) on RNA from 19 paired leiomyoma (Lyo) and myometrium (Myo) specimens, stratified by race/ethnicity (White: n = 7; Black: n = 12) and mediator complex subunit 12 (MED12) mutation status (mutated: n = 10; non-mutated: n = 9). Analysis identified 2,189 small non-coding RNAs (sncRNAs) with altered expression in Lyo compared to paired Myo (≥1.5-fold change), including small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs). Among these, 17 sncRNAs showed differential expression in the MED12-mutated group versus Myo, while minimal changes were observed in the non-mutated group. Additionally, 31 sncRNAs displayed differential expression in Black women compared to White women. For validation, five novel miRNAs (miR-19a-3p, miR-99a-5p, miR-3196, miR-499a-5p, and miR-30d-3p) and five piRNAs (piR-009295, piR-020326, piR-020365, piR-006426, and piR-020485) were analyzed in 51 paired Lyo samples using qRT-PCR. Reduced expression of the selected sncRNAs was confirmed in Lyo versus Myo, with miR-19a-3p, miR-3196, miR-30d-3p, piR-006426, and piR-020485 linked to MED12 status, while miR-499a-5p and miR-30d-3p were associated with race/ethnicity. These findings suggest that sncRNA dysregulation contributes to altered gene expression in Lyo, influenced by MED12 mutation and racial background.