AUTHOR=Catellani Cecilia , Ravegnini Gloria , Sartori Chiara , Righi Beatrice , Lazzeroni Pietro , Bonvicini Laura , Poluzzi Silvia , Cirillo Francesca , Predieri Barbara , Iughetti Lorenzo , Giorgi Rossi Paolo , Angelini Sabrina , Street Maria Elisabeth 

TITLE=Specific miRNAs Change After 3 Months of GH treatment and Contribute to Explain the Growth Response After 12 Months

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.896640

DOI=10.3389/fendo.2022.896640

ISSN=1664-2392

ABSTRACT=Context: There is growing evidence on the role of epigenetic regulation of growth, and miRNAs potentially play a role. 
Objective: to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months on treatment, and verify whether these early changes can predict growth response.
Design and methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC)>±1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response. 
Results: 16 miRNAs were up-regulated and 2 down-regulated at t+3 months. MiR-199a-5p (p=0.020), miR-335-5p (p=0.001), and miR-494-3p (p=0.026) were confirmed to be up-regulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters.
Conclusions: miR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months on GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response.