The novel circ_0084904/miR-802/MAL2 axis promotes the development of cervical cancer |
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| Institution: | 1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, PR China;2. Department of Anatomy and Histology, Faculty of Veterinary Science, University of Agriculture, Faisalabad, 38000, Punjab, Pakistan;3. Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China;4. Department of Theriogenology, Faculty of Veterinary Science, University of Agriculture, Faisalabad, 38000 Punjab, Pakistan;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. Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran;2. Institute of Pharmacology and Toxicology, University Medical Center, Georg August University, Göttingen, Germany;3. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;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. Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli studi della Campania “Luigi Vanvitelli”, Caserta, Italy;2. Dipartimento di Scienze e Tecnologie, Università degli studi del Sannio, Benevento, Italy |
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| Abstract: | Circular RNAs (circRNAs) have been identified as critical regulators in human cancers, including cervical cancer (CC). However, the precise action of circ_0084904 in cervical carcinogenesis remains to be elucidated. The levels of circ_0084904, microRNA (miR)-802, and Mal, T cell differentiation protein 2 (MAL2) were checked by quantitative real-time PCR (qRT-PCR) or western blot. Ribonuclease R (RNase R) and subcellular localization assays were used to detect the stability and localization of circ_0084904, respectively. Cell colony formation ability was assessed by colony formation assay. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion abilities were gauged by transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to determine the direct relationship between miR-802 and circ_0084904 or MAL2. The xenograft experiments were performed to evaluate the role of circ_0084904 in tumor growth in vivo. Circ_0084904 was markedly up-regulated in CC tissues and cell lines. Silencing endogenous circ_0084904 impeded cell colony formation, cell cycle progression, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0084904 targeted miR-802, and the effects of circ_0084904 silencing were mediated by miR-802. MAL2 was directly targeted and inhibited by miR-802, and MAL2 was a functional target of miR-802. Moreover, circ_0084904 modulated MAL2 expression via miR-802. Our study identified circ_0084904 as a novel oncogenic driver in CC depending on the modulation of the miR-802/MAL2 axis, establishing the notion that silencing of circ_0084904 might represent a promising targeted therapy for CC. |
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| Keywords: | Cervical cancer (CC) circ_0084904 miR-802 MAL2 Carcinogenesis |
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