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Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance.

Lin L, Du T, Huang J, Huang LL, Yang DZ - Chin. Med. J. (2015)

Bottom Line: The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated.Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).We identified and validated two miRNAs-miR-92a and miR-92b.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.

ABSTRACT

Background: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age. The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism. The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated. Micro-ribonucleic acids (miRNAs) have recently been shown to play a role in regulation of ovarian function. Our current study focused on the altered expression of miRNAs with PCOS.

Methods: Ovarian theca interna tissues were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection. Total RNA of all samples was extracted. We studied the repertoire of miRNAs in both PCOS and non-PCOS women by microarray hybridization. Bioinformatic analysis was performed for predicting targets of the differentially expressed miRNAs. Furthermore, selected miRNAs were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results: A total of 27 miRNAs were differentially expressed in PCOS patients with respect to the controls in our discovery evaluationand two (miR-92a and miR-92b) of them were significantly downregulated in PCOS women in followed validation (P < 0.05). Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).

Conclusions: MiRNAs are differentially expressed between PCOS patients and controls. We identified and validated two miRNAs-miR-92a and miR-92b. They are significantly downregulated and may be involved in the pathogenesis of PCOS.

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Related in: MedlinePlus

Strategies of selecting miRNAs. miRNA = Micro-ribonucleic acid; IRS-2 = insulin receptor substrate 2; GATA6 = GATA-binding factor 6.
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Figure 1: Strategies of selecting miRNAs. miRNA = Micro-ribonucleic acid; IRS-2 = insulin receptor substrate 2; GATA6 = GATA-binding factor 6.

Mentions: Using miRNA microarray analysis, we evaluated miRNA expression profiles of ovarian theca tissues of PCOS with IR patients and non-PCOS, non-IR controls. A total of 27 miRNAs were differentially expressed with a fold change of ≥1.5 or ≤0.67. Given that biological significance of miRNA deregulation relies on the effect upon their cognate protein-coding gene targets, we analyzed the predicted targets of the most significantly up- and downregulated miRNAs: miR-200a, miR-141, miR-200c, miR-502-3p, miR-32, miR-92a, miR-92b, miR-19b, miR-1, and let-7g. The analysis was done using four algorithms, TargetScan 6.2, PicTar, miRBase, and miRanda, which are commonly used to predict human miRNA gene targets. Prediction results [Figure 1 and Table 4] demonstrated that the putative target genes of the above miRNAs include CYP17, GATA6, and IRS-2.


Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance.

Lin L, Du T, Huang J, Huang LL, Yang DZ - Chin. Med. J. (2015)

Strategies of selecting miRNAs. miRNA = Micro-ribonucleic acid; IRS-2 = insulin receptor substrate 2; GATA6 = GATA-binding factor 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837833&req=5

Figure 1: Strategies of selecting miRNAs. miRNA = Micro-ribonucleic acid; IRS-2 = insulin receptor substrate 2; GATA6 = GATA-binding factor 6.
Mentions: Using miRNA microarray analysis, we evaluated miRNA expression profiles of ovarian theca tissues of PCOS with IR patients and non-PCOS, non-IR controls. A total of 27 miRNAs were differentially expressed with a fold change of ≥1.5 or ≤0.67. Given that biological significance of miRNA deregulation relies on the effect upon their cognate protein-coding gene targets, we analyzed the predicted targets of the most significantly up- and downregulated miRNAs: miR-200a, miR-141, miR-200c, miR-502-3p, miR-32, miR-92a, miR-92b, miR-19b, miR-1, and let-7g. The analysis was done using four algorithms, TargetScan 6.2, PicTar, miRBase, and miRanda, which are commonly used to predict human miRNA gene targets. Prediction results [Figure 1 and Table 4] demonstrated that the putative target genes of the above miRNAs include CYP17, GATA6, and IRS-2.

Bottom Line: The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated.Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).We identified and validated two miRNAs-miR-92a and miR-92b.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.

ABSTRACT

Background: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age. The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism. The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated. Micro-ribonucleic acids (miRNAs) have recently been shown to play a role in regulation of ovarian function. Our current study focused on the altered expression of miRNAs with PCOS.

Methods: Ovarian theca interna tissues were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection. Total RNA of all samples was extracted. We studied the repertoire of miRNAs in both PCOS and non-PCOS women by microarray hybridization. Bioinformatic analysis was performed for predicting targets of the differentially expressed miRNAs. Furthermore, selected miRNAs were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results: A total of 27 miRNAs were differentially expressed in PCOS patients with respect to the controls in our discovery evaluationand two (miR-92a and miR-92b) of them were significantly downregulated in PCOS women in followed validation (P < 0.05). Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).

Conclusions: MiRNAs are differentially expressed between PCOS patients and controls. We identified and validated two miRNAs-miR-92a and miR-92b. They are significantly downregulated and may be involved in the pathogenesis of PCOS.

Show MeSH
Related in: MedlinePlus