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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

Relative expression of miR-200a, miR-141, miR-200c, miR-502-3p, miR-32, miR-92a, miR-92b, miR-19b, miR-1, and let-7g in microarray (blue) and qRT-PCR (red). Up regulation miRNAs were represented as fold change ≤1 and down regulation ones as fold change ≤1 at the same time. The dotted lines represented the thresholds (≥1.5 and ≤0.67) of fold change we have set in our study for screening differentially expressed miRNAs. miRNA = Micro-ribonucleic acid; qRT-PCR = Quantitative reverse transcriptase polymerase chain reaction.
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Figure 2: Relative expression of miR-200a, miR-141, miR-200c, miR-502-3p, miR-32, miR-92a, miR-92b, miR-19b, miR-1, and let-7g in microarray (blue) and qRT-PCR (red). Up regulation miRNAs were represented as fold change ≤1 and down regulation ones as fold change ≤1 at the same time. The dotted lines represented the thresholds (≥1.5 and ≤0.67) of fold change we have set in our study for screening differentially expressed miRNAs. miRNA = Micro-ribonucleic acid; qRT-PCR = Quantitative reverse transcriptase polymerase chain reaction.

Mentions: To validate our array expression findings, 10 differentially expressed miRNAs (miR-1, miR-19b, miR-32, miR-92a, miR-92b, miR-141, miR-200a, miR-200c, miR-502-3p, and let-7g) were chosen for qRT-PCR analysis. The miRNAs were selected on the basis of their target genes. The trends for downregulation of miRNA expression were consistent in five of the 10 (miR-19b, miR-92a, miR-92b, miR-141, and 200a) qRT–PCR measurements [Figure 2 and Table 5].


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)

Relative expression of miR-200a, miR-141, miR-200c, miR-502-3p, miR-32, miR-92a, miR-92b, miR-19b, miR-1, and let-7g in microarray (blue) and qRT-PCR (red). Up regulation miRNAs were represented as fold change ≤1 and down regulation ones as fold change ≤1 at the same time. The dotted lines represented the thresholds (≥1.5 and ≤0.67) of fold change we have set in our study for screening differentially expressed miRNAs. miRNA = Micro-ribonucleic acid; qRT-PCR = Quantitative reverse transcriptase polymerase chain reaction.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Relative expression of miR-200a, miR-141, miR-200c, miR-502-3p, miR-32, miR-92a, miR-92b, miR-19b, miR-1, and let-7g in microarray (blue) and qRT-PCR (red). Up regulation miRNAs were represented as fold change ≤1 and down regulation ones as fold change ≤1 at the same time. The dotted lines represented the thresholds (≥1.5 and ≤0.67) of fold change we have set in our study for screening differentially expressed miRNAs. miRNA = Micro-ribonucleic acid; qRT-PCR = Quantitative reverse transcriptase polymerase chain reaction.
Mentions: To validate our array expression findings, 10 differentially expressed miRNAs (miR-1, miR-19b, miR-32, miR-92a, miR-92b, miR-141, miR-200a, miR-200c, miR-502-3p, and let-7g) were chosen for qRT-PCR analysis. The miRNAs were selected on the basis of their target genes. The trends for downregulation of miRNA expression were consistent in five of the 10 (miR-19b, miR-92a, miR-92b, miR-141, and 200a) qRT–PCR measurements [Figure 2 and Table 5].

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