title: The expression of the miR-25/93/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  AT was excised from 16 women with PCOS (eight with and eight without IR) and 15 non-PCOS (nine with and six without IR).
  
  
  METHODS
  Expression of MCM7 and miR-25/93/106b was measured in AT and 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.
authors.affiliation: Departments of Obstetrics/Gynecology (H.-L.W., S.H., T.Y.C., M.P.D., L.C.L., R.A., Y.-H.C.), Surgery (L.C.L.), and Medicine (R.A.), Institute of Molecular Medicine and Genetics (L.C.L.), and Neuroscience Program (L.C.L.), Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Hsiao-Li
authors.initials: HL
authors.lastname: Wu
authors.forename: Saleh
authors.initials: S
authors.lastname: Heneidi
authors.forename: Tung-Yueh
authors.initials: TY
authors.lastname: Chuang
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azziz
authors.forename: Yen-Hao
authors.initials: YH
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*; D064168:Minichromosome Maintenance Complex Component 7 / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism*
chemical_list: C542541:MIRN106 microRNA, human; C543351:MIRN25 microRNA, human; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7