Li Jin1, Qian Yang2, Chengliang Zhou3, Lanxin Liu1, Huihui Wang1, Min Hou1, Yimei Wu1, Fengtao Shi1, Jianzhong Sheng4, Hefeng Huang5. 1. International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China. 2. International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China; Karolinska Institutet Stockholm, Sweden. 3. Woman's Hospital, School of Medicine, Zhejiang University Zhejiang, China; Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China; Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China. 4. Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University Zhejiang, China. 5. International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China; Woman's Hospital, School of Medicine, Zhejiang University Zhejiang, China; Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China; Karolinska Institutet Stockholm, Sweden. Electronic address: huanghefg@sjtu.edu.cn.
Abstract
RESEARCH QUESTION: What is the expression pattern of long non-coding RNAs (lncRNA) in ovarian granulosa cells of women with polycystic ovary syndrome (PCOS) with or without hyperandrogenism? DESIGN: Microarray screening of lncRNA was conducted in ovarian granulosa cells collected from women with PCOS with hyperandrogenism (PCOS-T) or without hyperandrogenism (PCOS-N) and control participants, with four samples in each group. This was followed by hierarchy clustering, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Several candidate lncRNA were randomly selected for quantitative polymerase chain reaction validation in another 54 patients. To predict the regulatory effect of lncRNA on hyperandrogenism, a co-expression network was plotted using differentially hexpressed lncRNA with statistical significance (≥ twofold; P < 0.05) in PCOS-T compared with PCOS-N. RESULTS: A total of 3000 and 1030 differentially expressed lncRNA (≥ twofold change) were detected in PCOS-T compared with control and PCOS-N, respectively. A total of 1361 differentially expressed lncRNA were detected in PCOS-N compared with controls. Corticotropin releasing hormone binding protein is consistently the up-regulated lncRNA with the highest fold-change in PCOS-T compared with either control or PCOS-N. Gene ontology and pathway analysis showed that dysregulated lncRNA in PCOS-T have a regulatory role in mitochondrial function by interacting with transcription factors such as YY1 and SIX5. CONCLUSIONS: The expression patterns of lncRNA in women with PCOS were ascertained by microarray. Many lncRNA were differentially expressed in PCOS-T compared with PCOS-N, suggesting that they may play a key role in steroid genesis and metabolism.
RESEARCH QUESTION: What is the expression pattern of long non-coding RNAs (lncRNA) in ovarian granulosa cells of women with polycystic ovary syndrome (PCOS) with or without hyperandrogenism? DESIGN: Microarray screening of lncRNA was conducted in ovarian granulosa cells collected from women with PCOS with hyperandrogenism (PCOS-T) or without hyperandrogenism (PCOS-N) and control participants, with four samples in each group. This was followed by hierarchy clustering, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Several candidate lncRNA were randomly selected for quantitative polymerase chain reaction validation in another 54 patients. To predict the regulatory effect of lncRNA on hyperandrogenism, a co-expression network was plotted using differentially hexpressed lncRNA with statistical significance (≥ twofold; P < 0.05) in PCOS-T compared with PCOS-N. RESULTS: A total of 3000 and 1030 differentially expressed lncRNA (≥ twofold change) were detected in PCOS-T compared with control and PCOS-N, respectively. A total of 1361 differentially expressed lncRNA were detected in PCOS-N compared with controls. Corticotropin releasing hormone binding protein is consistently the up-regulated lncRNA with the highest fold-change in PCOS-T compared with either control or PCOS-N. Gene ontology and pathway analysis showed that dysregulated lncRNA in PCOS-T have a regulatory role in mitochondrial function by interacting with transcription factors such as YY1 and SIX5. CONCLUSIONS: The expression patterns of lncRNA in women with PCOS were ascertained by microarray. Many lncRNA were differentially expressed in PCOS-T compared with PCOS-N, suggesting that they may play a key role in steroid genesis and metabolism.