MiR-106a increases granulosa cell viability and is down-regulated in women with diminished ovarian reserve.

MiR-106a increases granulosa cell viability and is down-regulated in women with diminished ovarian reserve.

J Clin Endocrinol Metab. 2018 Mar 23;:

Authors: Hong L, Peng S, Li Y, Fang Y, Wang Q, Klausen C, Yin C, Wang S, Leung PCK, Yang X

Abstract
Context: Women with diminished ovarian reserve (DOR) suffer from reduced fertility, cardiovascular events and osteoporosis. Though differential microRNA (miRNA) expression has been described in several ovarian disorders, little is known about the role of miRNAs in the pathogenesis of DOR.
Objective: Identify differentially expressed miRNAs in DOR and explore the role of miR-106a in human granulosa cell proliferation.
Design: MiRNA microarray (n=3) and RT-qPCR (n=30) were used to examine miRNA expression in serum and granulosa cells from normal cycling and DOR women. Primary human granulosa cells were treated alone or in combination with miR-106a mimic, miR-106a inhibitor, apoptosis signal-regulating kinase 1 (ASK1) siRNA or p38 MAPK inhibitor (SB203580) prior to assessment of cell viability and apoptosis. Western blot was used to measure ASK1 protein and phosphorylation/activation of p38 MAPK. Binding of miR-106a to ASK1 mRNA was examined by 3'UTR luciferase analysis.
Results: 15 miRNAs were differentially expressed (n=30) and miR-106a was down-regulated in serum and granulosa cells of DOR women. MiR-106a mimic increased cell viability and attenuated apoptosis, whereas the converse occurred following treatment with miR-106a inhibitor. MiR-106a suppressed ASK1 expression by directly targeting its 3'UTR. MiR-106a inhibitor increased p38 MAPK phosphorylation/activation, and this effect was abolished by treatment with ASK1 siRNA. Whereas knockdown of ASK1 abolished the effects of miR-106a inhibitor on cell viability/apoptosis, pre-treatment with SB203580 did not significantly alter the effects of miR-106a inhibitor.
Conclusions: Down-regulation of miR-106a may contribute to the pathogenesis of DOR by reducing granulosa cell viability and promoting apoptosis via enhanced ASK1 signaling.

PMID: 29590425 [PubMed - as supplied by publisher]

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