Abu-Halima M, Oberhoffer FS, El Rahman MA, Jung AM, Zemlin M, Rohrer TR, Kahraman M, Keller A, Meese E, Abdul-Khaliq H.
PLoS One. 2020 Apr 9;15(4):e0231402. doi: 10.1371/journal.pone.0231402. eCollection 2020.
PMID: 32271829 Free PMC Article
Select item 32313642
Background: Turner syndrome (TS) is a chromosomal disorder, in which a female is partially or entirely missing one of the two X chromosomes, with a prevalence of 1:2500 live female births. The present study aims to identify a circulating microRNA (miRNA) signature for TS patients with and without congenital heart disease (CHD).
Methods: Microarray platform interrogating 2549 miRNAs were used to detect the miRNA abundance levels in the blood of 33 TS patients and 14 age-matched healthy volunteer controls (HVs). The differentially abundant miRNAs between the two groups were further validated by RT-qPCR.
Results: We identified 60 differentially abundant miRNA in the blood of TS patients compared to HVs, from which, 41 and 19 miRNAs showed a higher and a lower abundance levels in TS patients compared to HVs, respectively. RT-qPCR confirmed the significantly higher abundance levels of eight miRNAs namely miR-374b-5p, miR-199a-5p, miR-340-3p, miR-125b-5p, miR-30e-3p, miR-126-3p, miR-5695, and miR-26b-5p in TS patients as compared with the HVs. The abundance level of miR-5695 was higher in TS patients displaying CHD as compared to TS patients without CHD (p = 0.0265; log2-fold change 1.99); whereas, the abundance level of miR-126-3p was lower in TS patients with congenital aortic valve disease (AVD) compared to TS patients without BAV (p = 0.0139, log2-fold change 1.52). The clinical feature statistics revealed that miR-126-3p had a significant correlation with sinotubular junction Z-score (r = 0.42; p = 0.0154).
Conclusion: The identified circulating miRNAs signature for TS patients with manifestations associated with cardiovascular diseases provide new insights into the molecular mechanism of TS that may guide the development of novel diagnostic approaches.
Fig 1. Validation of eight differentially expressed miRNAs in the blood of patients with TS (n = 33) compared to HVs (n = 14) as determined by RT-qPCR (P < 0.05). Mean ΔCt (Lower ΔCt, higher abundance level). RNAU6B as an endogenous control for normalization, Unpaired-two-tailed t-tests and median ± standard deviation (STDV) were used to evaluate differences in abundance. * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001.
Fig 2. Differentially expressed miRNA in TS patients with (n = 12) and without CHD (n = 21), and patients with (n = 10) and without AVD (n = 23). Mean ΔCt (Lower ΔCt, higher abundance level). RNAU6B as an endogenous control for normalization, Unpaired-two-tailed t-tests and median ± standard deviation (STDV) were used to evaluate differences in abundance. * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001.
Fig 3. Target network for the five validated miRNAs in brown, validated target genes are presented in blue.