Hsa_circ_0001495 contributes to cervical cancer progression by targeting miR-526b-3p/TMBIM6/mTOR axis |
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| Affiliation: | 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 Animal Science and Technology, Beijing University of Agriculture, Beijing, 102206, China;2. College of Economics and Management, Beijing University of Agriculture, Beijing, 102206, China;3. China National Biotec Group Company Limited, Beijing, 102206, China;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. Department of Science and Education, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, PR China;2. The Reproductive Medical Center, The Second Nanning People’s Hospital, Nanning, 530031, Guangxi, PR China;3. Department of Reproductive Medicine, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, PR China;4. Department of Clinical Laboratory, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, PR China;5. Guangxi University of Chinese Medicine, Nanning, 530200, Guangxi, PR 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 |
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| Abstract: | Cervical cancer (CC) is a common gynecological malignant tumor, causing poor survival rate. Circular RNAs (circRNAs) are abundantly expressed in CC with their stable loop structure. However, the underlying mechanism and biological function of circRNAs remained unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay, we measured the expression of hsa_circ_0001495, miR-526b-3p, and transmembrane Bax inhibitor motif containing 6 (TMBIM6) in CC tissues and cells. The relationship between miR-526b-3p and hsa_circ_0001495 or TMBIM6 was investigated by bioinformatics analysis, dual-luciferase and RIP analysis. Enzyme linked immunosorbent assay (ELISA) was conducted to evaluate glucose consumption and lactate production. 5-ethynyl-2′-deoxyuridine (EDU) assay were used to test cell proliferation. Cell apoptosis was analyzed by using flow cytometry assay. Transwell and wound-healing assays were used to measure cell invasion and migration. The expression of proteins was examined by western blot. Xenograft assay was applied to detect the effect of hsa_circ_0001495 in vivo. Our finding showed that hsa_circ_0001495 and TMBIM6 expression were upregulated, while miR-526b-3p was downregulated in CC tissues and cell lines. Hsa_circ_0001495 knockdown or TMBIM6 knockdown suppressed cell proliferation, migration, glycolysis, while promoted cell apoptosis in vitro, and hsa_circ_0001495 silence curbed tumor growth in vivo. Beside, hsa_circ_0001495 exerted its function in CC by positively regulating TMBIM6. Furthermore, hsa_circ_0001495 acted as a sponge for miR-526b-3p to regulate TMBIM6 expression. Hsa_circ_0001495/miR-526b-3p/TMBIM6 axis also regulated the phosphorylation of mammalian target of rapamycin (mTOR) in CC cells. In summary, hsa_circ_0001495 regulated the progression of CC by regulating miR-526b-3p/TMBIM6/mTOR pathway. |
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| Keywords: | Cervical cancer Hsa_circ_0001495 MiR-526b-3p TMBIM6 Glycolysis |
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