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. 2016 May;13(5):3920-8.
doi: 10.3892/mmr.2016.5019. Epub 2016 Mar 21.

Transcription factor‑microRNA synergistic regulatory network revealing the mechanism of polycystic ovary syndrome

Hai-Ying Liu  1 , Yu-Ling Huang  1 , Jian-Qiao Liu  1 , Qing Huang  1
Affiliations

Transcription factor‑microRNA synergistic regulatory network revealing the mechanism of polycystic ovary syndrome

Hai-Ying Liu et al. Mol Med Rep. 2016 May.

Abstract

Polycystic ovary syndrome (PCOS) is the most common type of endocrine disorder, affecting 5‑11% of women of reproductive age worldwide. Transcription factors (TFs) and microRNAs are considered to have crucial roles in the developmental process of several diseases and have synergistic regulatory actions. However, the effects of TFs and microRNAs, and the patterns of their cooperation in the synergistic regulatory network of PCOS, remain to be elucidated. The present study aimed to determine the possible mechanism of PCOS, based on a TF‑microRNA synergistic regulatory network. Initially, the differentially expressed genes (DEGs) in PCOS were identified using microarray data of the GSE34526 dataset. Subsequently, the TFs and microRNAs which regulated the DEGs of PCOS were identified, and a PCOS‑associated TF‑microRNA synergistic regulatory network was constructed. This network included 195 DEGs, 136 TFs and 283 microRNAs, and the DEGs were regulated by TFs and microRNAs. Based on topological and functional enrichment analyses, SP1, mir‑355‑5p and JUN were identified as potentially crucial regulators in the development of PCOS and in characterizing the regulatory mechanism. In conclusion, the TF‑microRNA synergistic regulatory network constructed in the present study provides novel insight on the molecular mechanism of PCOS in the form of synergistic regulated model.

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Figures

Figure 1
Figure 1
TF-DEG network. Circular nodes represent DEGs and red triangle nodes represent TFs. Nodes are connected if the DEGs are the targets of the corresponding TF. DEG, differentially expressed gene; TF, transcription factor.
Figure 2
Figure 2
microRNA-DEG network. The circular nodes represent DEGs and the red square nodes represent microRNAs. Nodes are connected if the DEGs are the targets of the corresponding microRNA. DEG, differentially expressed gene.
Figure 3
Figure 3
TF-microRNA synergistic regulatory network. The circular nodes represent DEGs, the red triangle nodes represent TFs and the blue square nodes represent microRNAs. The nodes are connected if the nodes are the targets of the corresponding microRNA of TFs. DEG, differentially expressed gene; TF, transcription factor.
Figure 4
Figure 4
Sub-networks of (A) SP1, (B) mir-355-5p and (C) JUN. The circular nodes represent differentially expressed genes, the red triangle nodes represent transcription factors and the blue square nodes represent microRNAs. The nodes are connected if the nodes are the targets of the corresponding microRNA of transcription factors.
Figure 5
Figure 5
Local region of WNT signaling pathways, in which JUN is located. The red nodes represent differentially expressed genes of polycystic ovary syndrome. CBP, cAMP response element-binding protein; +p, phosphorylation; SMAD, small mothers against decapentaplegic; NLK, nemo-like kinase; CtBP, C-terminal binding protein 1; TCF/LEF, T-cell factor/lymphoid enhancer factor; PPAR5, peroxisome proliferator-activated receptor 5; TGF-β, transforming growth factor-β.
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