MicroRNA-223 Expression is Upregulated in Insulin Resistant Human Adipose Tissue.
MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT) from women with polycystic ovary syndrome (PCOS) or controls with insulin resistance (IR) revealed a differentially expressed microRNA (miRNA) profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4) expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3' untranslated region (3'UTR). In conclusion, in AT miR-223 is an IR-related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders.
Department of Obstetrics/Gynecology, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Tung-Yueh
TY
Chuang
Department of Obstetrics/Gynecology, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Hsiao-Li
HL
Wu
Department of Biostatistics, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Chen-Chun
CC
Chen
Department of Surgery, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Gloria Mabel
GM
Gamboa
Department of Obstetrics/Gynecology, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA ; Section of Reproductive Endocrinology, Infertility & Genetics, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA ; Institute of Molecular Medicine and Genetics, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA ; Neuroscience Program, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Lawrence C
LC
Layman
Department of Obstetrics/Gynecology, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Michael P
MP
Diamond
Department of Obstetrics/Gynecology, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA ; Department of Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Ricardo
R
Azziz
Department of Obstetrics/Gynecology, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
Yen-Hao
YH
Chen
D020413:3' Untranslated Regions; D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D020413:3' Untranslated Regions; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C525067:MIR223, human; C543350:MIRN93 microRNA, human; C495692:SLC2A4 protein, human