The Role of Serum MicroRNA-6767-5p as a Biomarker for the Diagnosis of Polycystic Ovary Syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, and the underlying molecular mechanisms are not clear. To date, few studies have been conducted on the altered expression of serum microRNAs (miRNAs) in women with PCOS. The present study was performed to examine the role of the serum miRNA as a biomarker for the diagnosis of PCOS and its relationship with metabolic and reproductive traits.


METHODS
A cross-sectional comparison was made in 21 women with PCOS and age- and body mass index (BMI)- matched 21 healthy women in an academic center laboratory between December 2008 and October 2010. We selected miRNAs that were more than 1.5-fold up-regulated or less than 0.67-fold down-regulated in women with PCOS compared with controls using the SurePrint G3 Human miRNA Microarray. Subsequently, we validated the relative expression of the miRNAs using TaqMan quantitative real-time polymerase chain reaction (RT-qPCR) assays.


RESULTS
Serum miRNA-4522, miRNA-324-3p, and miRNA-6767-5p were down-regulated in women with PCOS compared with controls in the microarray analysis. Among these miRNAs, serum miRNA-6767-5p was validated (fold change in women with PCOS/controls = 0.39, P-value<0.05) by RT-qPCR. The miRNA-6767-5p was negatively associated with fasting glucose (β = -0.370) and positively associated with the number of menses per year (β = 0.383) after adjustment for age and BMI (Ps<0.05). Genes targeted by miRNA-6767-5p were involved in the cell cycle and the immune system.


CONCLUSIONS
Serum miRNA-6767-5p may be a novel candidate as a molecular biomarker in the diagnosis of PCOS and may participate in the development of the metabolic and reproductive traits of PCOS.
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Do Kyeong
http://orcid.org/0000-0003-2101-6661
DK
Song
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Yeon-Ah
YA
Sung
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Hyejin
H
Lee
Nat Rev Genet. 2004 Jul;5(7):522-31
15211354
J Assist Reprod Genet. 2014 Mar;31(3):355-62
24390626
J Cell Physiol. 2009 May;219(2):415-20
19194990
Genes (Basel). 2014 Aug 25;5(3):684-708
25158044
Circ Res. 2012 Feb 3;110(3):483-95
22302755
Diabetes. 2013 Jul;62(7):2278-86
23493574
J Clin Endocrinol Metab. 2004 Nov;89(11):5592-6
15531516
Methods. 2001 Dec;25(4):402-8
11846609
Cell Physiol Biochem. 2014;33(5):1304-15
24802714
Cell Res. 2008 Oct;18(10):997-1006
18766170
Semin Reprod Med. 2008 Nov;26(6):469-78
18951329
Hum Reprod Update. 2012 Mar-Apr;18(2):146-70
22064667
Hum Reprod Update. 2004 Mar-Apr;10(2):119-33
15073142
Diabetes Metab J. 2014 Aug;38(4):302-10
25215277
J Clin Endocrinol Metab. 2013 Jul;98(7):3068-79
23666971
Diabetes Care. 2000 Mar;23(3):295-301
10868854
Hum Reprod Update. 2003 Nov-Dec;9(6):505-14
14714587
J Ovarian Res. 2015 Aug 01;8:51
26232057
Nat Rev Endocrinol. 2011 Apr;7(4):219-31
21263450
Cell. 1993 Dec 3;75(5):843-54
8252621
Nature. 2008 Sep 4;455(7209):64-71
18668037
PLoS One. 2014 Apr 14;9(4):e94167
24732316
Hum Fertil (Camb). 2015 Mar;18(1):22-9
25268995
EXCLI J. 2015 Feb 02;14:190-8
26535032
J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9
15181052
J Clin Endocrinol Metab. 1999 Oct;84(10):3666-72
10523012
Nat Rev Cancer. 2006 Nov;6(11):857-66
17060945
N Engl J Med. 2009 Sep 17;361(12):1152-63
19657112
Cell Tissue Res. 2012 Sep;349(3):679-90
22842772
J Ovarian Res. 2012 Feb 09;5:8
22321819
Mol Cell Endocrinol. 2015 Mar 15;404:26-36
25622783
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8
18663219
J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8
10902790
Fertil Steril. 2011 Mar 1;95(3):1048-58.e1-2
21168133
Nature. 2000 Nov 2;408(6808):86-9
11081512
J Clin Endocrinol Metab. 2013 Nov;98(11):E1835-44
24037889
Diabetes. 2011 Jul;60(7):1825-31
21709277
N Engl J Med. 2005 Mar 24;352(12):1223-36
15788499
Adv Clin Chem. 2015;71:25-45
26411410