Abnormal MicroRNA Expression Profile Mav Result In GC Dysfunction In PCOS Patients

Polycystic ovary syndrome is among the most common endocrine disease. It is a heterogeneous disease with severe consequences which may finally lead to infertility and other endocrine diseases. The ovarian dysfunction and its related disorder of endocrine and metabolism are believed to be the pathological mechanism of this disease. Increasing evidence has demonstrated the relationship between aberrantly expressed microRNA profiles and ovarian dysfunction. We thus investigated the expression profiles of microRNAs in PCOS patients, by use of microRNA microarray. We identified52differentially expressed microRNAs in patients with PCOS, of which38were up-regulated while the other14were down-regulated. We found that miR-145-3p, miR-345-5p and miR-375were among the most up-regulated. Quantitative real-time PCR verified that the expression of the three microRNAs were significantly increased in PCOS patients’ granulosa cell. To confirm which gene may be the target gene of miR-375, we performed an another quantitative real-time PCR to find out that Epidermal Growth Factor Receptor (EGFR) and Janus Kinase2(JAK2) may be the target gene of miR-375. We then observed that overexpression of miR-375in primary granulosa cell and KGN cell line reduced the expression of EGFR in mRNA and protein level, suggesting that EGFR may be a target gene of miR-375. Moreover, miR-375inhibitor can partially restore the suppression from miR-375. EGFR and its downstream signalling factor JAK2and Signal Transducer and Activitor of Transcription3(STAT3) are deeply and positively related. By treatment of KGN with AG490(a specific inhibitor of JAK2) and or androstenedione, we found that the down-regulated JAK2/STAT3pathway may furthermore effect the CYP19al expression in mRNA level. Taken together, we propose that miR-375is exerting a vital role in the pathogenesis of PCOS via modulating the endocrine homeostasis in patients.