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Functional implications of miR-145/RCAN3 axis in the progression of cervical cancer
Institution:1. Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, PR China;2. Department of Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, PR China;3. Department of Oncology, People Hospital Affiliated to Hebei Medical University, Shijiazhuang, 050000, PR China;1. Shanghai JIAI Genetics & IVF Institute, Obstetrics & Gynecology Hospital of Fudan University, Shanghai 200011, China;2. Shanghai Key Laboratory for Female Reproductive Endocrine-Related Diseases, Institute of Reproductive and Development, Fudan University, Shanghai 200433, China;1. Department of Animal Reproduction and Veterinary Radiology, College of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu, São Paulo, Brazil;2. Paranaense University, Department of Animal Reproduction, Umuarama, Paraná, Brazil;3. Santo Amaro University, Department of Animal Reproduction, São Paulo, São Paulo, Brazil;4. Laboratory of Animal Reproduction, Embrapa Genetic Resources and Biotechnology, Brasília, Distrito Federal, Brazil;1. Department of Reproductive Center, First Affiliated Hospital ofGuangxi Medical University, Nanning, Guangxi, 530021, China;2. Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, China;3. Reproductive Medicine Center, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, 545005, China;1. Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia;2. I-PPerFORM, Universiti Teknologi MARA, Malaysia;1. Department of Urology, St. Marianna University of Medicine, 2 -16-1 Sugao, Miyamae, Kawasaki, Kanagawa, 216-8511, Japan;2. College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0890, Japan;3. Laboratory of Animal Reproduction, Faculty of Bioscience and Bioindustry, Tokushima University, Ishii, Myozai-gun, Tokushima, 779-3233, Japan;1. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Abstract:Cervical cancer, as the second leading cause of death in women malignant tumor, is not optimistic about survival rate and late recurrence rate. RCAN3 has been reported to function in a variety of diseases, but its relationship with cervical cancer has not been reported. This study aimed to investigate whether RCAN3 contributes to the development of cervical cancer and its mechanism. RCAN3 expression was analyzed in 306 cervical cancer tissues and 13 normal healthy tissues from TCGA and GTEX databases. Kaplan-Meier analysis and Cox regression analysis were carried out to assess the potential function of RCAN3. Subsequently, the upstream regulatory miRNA of RCAN3 was predicted by bioinformatics and confirmed using dual luciferase reporter assay. CCK-8, colony formation assay, transwell assay were used for functional analysis of miR-145/RCAN3 axis in vitro. The results showed that RCAN3 was highly expressed in cervical cancer tissues, leading to poor prognosis, and could be used as a prognostic factor for cervical cancer. MiR-145 directly targeted RCAN3, which was lowly expressed in cervical cancer tissues and cell lines, and the higher the miR-145 expression, the longer the survival time of patients. Finally, from the functional experiments results we can see that miR-145 can inhibit the proliferation, migration and invasion of cervical cancer cells, but overexpression of RCAN3 can reverse miR-145-mediated inhibition. To sum up, miR-145/RCAN3 axis may serve as a potential therapeutic target to regulate the progression of cervical cancer.
Keywords:Cervical cancer  RCAN3  miR-145  Target
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