Wang Mingming, Sun Jing, Xu Bo, Chrusciel Marcin, Gao Jun, Bazert Maciej, Stelmaszewska Joanna, Xu Yunyun, Zhang Hongwen, Pawelczyk Leszek, Sun Fei, Tsang Suk Ying, Rahman Nafis, Wolczynski Slawomir, Li Xiangdong

Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China.| State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.| State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.| Center for Reproductive Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China.| Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland.| Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China.| State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.| Department of Infertility and Reproductive Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.| Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.| Department of General Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.| Department of General Surgery, 306th Hospital of People's Liberation Army of China, Beijing, China.| Department of Infertility and Reproductive Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.| School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.| School of Life Science and State Key Laboratory of Agro-Biotechnology, Chinese University of Hong Kong, Hong Kong 999077, China.| Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland.| Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.| Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.| Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China.| State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

Endocrinology. 2018 Jan 1;159(1):297-309. doi: 10.1210/en.2017-00219.

The goal of this study was to characterize the function of microRNA-27a-3p (miR-27a-3p) in polycystic ovary syndrome (PCOS). miR-27a-3p expression was analyzed in excised granulosa cells (GCs) from 21 patients with PCOS and 12 normal patients undergoing in vitro fertilization cycle treatments and in 17 nontreated cuneiform ovarian resection PCOS samples and 13 control ovarian samples from patients without PCOS. We found that the expression of miR-27a-3p was significantly increased in both excised GCs and the ovaries of patients with PCOS compared with the controls. Insulin treatment of the human granulosa-like tumor cell line (KGN) resulted in decreased downregulated expression of miR-27a-3p, and this effect appeared to be mediated by signal transducer and activator of transcription STAT1 and STAT3. The overexpression of miR-27a-3p in KGN cells inhibited SMAD5, which in turn decreased cell proliferation and promoted cell apoptosis. After KGN cells were stimulated with insulin for 48 hours, there was increased expression of SMAD5 protein and decreased apoptosis. Additionally, knockdown/overexpression of SMAD5 in KGN cells reduced/increased cell number and promoted/inhibited cell apoptosis. Insulin-stimulated primary GCs isolated from patients with PCOS, in contrast to normal GCs or KGN cells, did not exhibit decreased miR-27a-3p expression. The differences in the expression levels in KGN cells and human PCOS GCs are likely explained by increased miR-27a-3p expression in the GCs caused by insulin resistance in PCOS. Taken together, our data provided evidence for a functional role of miR-27a-3p in the GCs' dysfunction that occurs in patients with PCOS.