SKP2 regulates ZEB1 expression and stimulates eutopic endometrial stromal cell invasion and proliferation of adenomyosis |
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| Institution: | 1. Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, China;2. Department of Dermatology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, China;3. Department of Medical Imaging, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 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. Laboratory of Reproductive Neuroendocrinology, Department of Zoology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan;2. Department of Zoology, Hafiz Hayat Campus, University of Gujrat, Gujrat, Pakistan;3. Laboratory of Microbiology and Immunology, Department of Zoology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan;1. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;4. Women''s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey;2. Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA;1. Department of Gynecologic Oncology, Shaanxi Provincial Cancer Hospital, Xi’an 710061, China;2. Department of Gastrointestinal Oncology, Shaanxi Provincial Cancer Hospital, Xi’an 710061, China |
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| Abstract: | Though endometriosis is benign, however, it shares certain characteristics with cancers, such as the ability to invade and metastasize. Previous studies have demonstrated that S-phase kinase associated protein2 (SKP2) promotes invasion, tumorigenesis, and metastasis. However, its correlation with adenomyosis is unclear. Herein, we aimed to look into SKP2 expression patterns and regulatory effects on endometrial stromal cell (ESC) proliferation and invasion, and its internal mechanism in adenomyosis. Western blot, qRT-PCR, and immunochemistry were carried out for detecting SKP2 and ZEB1 expression in ESC of adenomyosis and adenomyosis endometrial tissue. The primary ESCs were identified using immunofluorescence. SKP2 knockdown was accomplished in vitro by transfecting a particular lentivirus vector. The colony formation and CCK-8 assays were carried out for assessing cell proliferation, while cell invasion potential was assessed using the transwell assay. Both SKP2 and ZEB1 were found to be significantly upregulated in adenomyosis endometrial tissue. Knockdown of SKP2 inhibited adenomyotic ESC invasion and proliferation. Further experiments showed that knocking out SKP2 reduced ZEB1 expression in adenomyotic ESCs. Our results showed that SKP2 could regulate ZEB1 expression, and increased SKP2 may play a role in the pathogenesis of adenomyosis and stimulating ESC proliferation and invasion. |
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| Keywords: | Adenomyosis SKP2 ZEB1 Cell invasion Cell proliferation Endometrial stromal cell |
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