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CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179
Institution:1. Department of Gynecology, Changxing People’s Hospital of Chongming District, Shanghai, China;2. Department of Gynecology, Jiaojiang Maternal and Child Health Hospital, Taizhou City, Zhejiang, China;3. Department of Ultrasound, Jiaojiang Maternal and Child Health Hospital, Taizhou City, Zhejiang, China;4. Department of Gynaecology, Lishui Hospital of Traditional Chinese Medicine, Lishui, Zhejiang, China;5. Department of Gynecology, Huzhou Maternity & Child Health Care Hospital, Huzhou, Zhejiang, China;6. Department of Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;1. Laboratorio de Medicina Reproductiva, Universidad Nacional de Rosario, Suipacha 531, C.P: 2000, Rosario, Santa Fe, Argentina;2. Consejo de Investigaciones de la Universidad Nacional de Rosario (CIUNR), Rosario, Santa Fe, Argentina;3. Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Rosario, Santa Fe, Argentina;1. College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, Gansu, China;2. Gansu Key Laboratory of Animal Generational Physiology and Reproductive Reg-ulation, China;1. Laboratory of Genetics and Evolution, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland;2. Forensic Genetics Section, Institute of Forensic Research, Krakow, Poland;3. Deptartment of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland;4. Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany;5. Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences Jastrz?biec, Magdalenka, Poland;1. Reproductive Medicine Center of the 1st Hospital of Lanzhou University, #1 Donggang West Road, Lanzhou, 730000, Gansu, People’s Republic of China;2. Key Laboratory for Reproductive Medicine and Embryo of Gansu, #1 Donggang West Road, Lanzhou, 730000, Gansu, People’s Republic of China;3. Gansu Provincial Hospital, #204 Donggang West Road, Lanzhou, 730000, People’s Republic of China;4. College of Life Science, Northwest Normal University, #967 Anning East Road, Lanzhou, 730070, Gansu, People’s Republic of China;1. Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, 410011, China;2. Department of Clinical Medicine, Harbin Medical University, Harbin, 150081, China
Abstract:Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.
Keywords:Polycystic ovary syndrome  circ_0043533  miR-1179  Insulin resistance
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