Altered miR-186 and miR-135a contribute to granulosa cell dysfunction by targeting ESR2: A possible role in polycystic ovary syndrome
Autor: | Guo Yu, Yan Li, Yuxia Song, Lijing Wan, Yungai Xiang, Li Tan |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Adult medicine.medical_specialty Granulosa cell Estrogen receptor 030209 endocrinology & metabolism Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Cell Line Tumor microRNA Gene expression medicine Estrogen Receptor beta Humans Luciferase Molecular Biology 3' Untranslated Regions Granulosa Cells Base Sequence Estrogens Polycystic ovary Pathophysiology MicroRNAs 030104 developmental biology Gene Expression Regulation Apoptosis Female hormones hormone substitutes and hormone antagonists Polycystic Ovary Syndrome |
Zdroj: | Molecular and cellular endocrinology. 494 |
ISSN: | 1872-8057 |
Popis: | MicroRNAs (miRNAs) are a group of negative regulators of gene expression that function at the posttranscriptional level. Dysregulation of miRNAs is involved in many pathophysiological processes, including polycystic ovary syndrome (PCOS). In this study, we first detected the expression levels of 6 candidate miRNA in granulosa cells (GCs) from 63 women with PCOS and 20 healthy controls. We found that miR-186 and miR-135a were overexpressed in GCs from PCOS patients. Subsequently, the direct targets of miR-186 and miR-135a were predicted using bioinformatics analysis and verified by luciferase assays and immunoblotting. The present study determined that miR-186 and miR-135a repressed ESR2 expression in GCs, which further inhibited CDKN1A expression, promoted GC proliferation and repressed GC apoptosis. Meanwhile, the levels of miR-186 and miR-135a in GCs were found to positively correlate with serum estradiol levels in patients with PCOS. Furthermore, estradiol treatment directly increased miR-186 and miR-135a levels in KGN and primary GCs, which provides new insight into understanding the pathophysiology of PCOS. |
Databáze: | OpenAIRE |
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