The expression of the miR-25/93/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome

Hsiao Li Wu, Saleh Heneidi, Tung Yueh Chuang, Michael P. Diamond, Lawrence C. Layman, Ricardo Azziz, Yen Hao Chen

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Context: In adipose tissue (AT) micro-RNA-93 (miR-93) is significantly overexpressed in polycystic ovary syndrome (PCOS) women and non-PCOS women with insulin resistance (IR). Overexpressed miR-93 directly inhibits glucose transporter isoform 4, impairing both glucose metabolism and insulin sensitivity. The mechanisms behind increased miR-93 expression are unclear. Objective: Our objective was to determine whether miR-93 expression is concordant with its host gene, MCM7, which contains the miR-25/93/106b gene cluster. Patients: AT was excised from 16 women with PCOS (eight with and eight without IR) and 15 non-PCOS (nine with and six without IR). Main Outcome Measures: Expression of MCM7 and miR-25/93/106b was measured inATand 3T3-L1 cells. Results: MCM7 expression was lower in both non-PCOS/IR and PCOS women and tended to be lowest in women with PCOS and IR. Overall, the expression of MCM7 in human AT was negatively associated with miR-93 expression and with increased subject IR. Additionally, miR-25 and miR-106b expression is uncoupled from the MCM7 host gene and are positively correlated with IR, although no PCOS-specific difference was observed. MCM7 expression appears to be negatively correlated with increasing fasting glucose. In 3T3-L1 adipocytes, increasing glucose had no effect on miR-93 or miR-25, although it reduced MCM7 and increased miR-106b expression in a dose-dependent fashion. In turn, in 3T3-L1 adipocytes, increasing insulin had no effect on either MCM7 or miR-25/93/106b expression. Conclusions: Our data suggest that the expression of MCM7 and miR-93/25 is PCOS and IR related, whereas that of miR-106b is related to IR only. In 3T3-L1 adipocytes, neither hyperglycemia nor hyperinsulinemia altered the expression of miR-93 or miR-25, although increasing glucose levels down-regulated MCM7 and paradoxically increased that of miR-106b expression. The expression of the miR-25/93/106b family may be regulated through mechanisms distinct from its host gene, MCM7. Finally, our studies suggest potential epigenetic mechanisms for both IR and PCOS.

Original languageEnglish (US)
Pages (from-to)E2754-E2761
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number12
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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