MicroRNA-129-5p suppresses proliferation,migration and invasion of retinoblastoma cells through PI3K/AKT signaling pathway by targeting PAX6 |
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Affiliation: | 1. Key Laboratory of Zoonosis, Ministry of Education Institutes, College of Veterinary Medicine, Jilin University, Changchun 130062, People’s Republic of China;2. Department of Genetic Medicine Weill Medical College of Cornell University, New York, NY 10065, USA;3. Department of Colorectal and Stomach Cancer Surgery of Jilin Cancer Hospital, Changchun 130000, PR China;4. Jilin Center for Disease Control, Changchun 130062, PR China;1. Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611, USA;2. Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA;3. Departments of Ophthalmology and Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA;4. Division of Hematology, Oncology, and Stem Cell Transplantation, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA;5. Division of Ophthalmology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA;6. Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA;7. Biostatistics Research Core, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611, USA;1. Department of Ophthalmology, the First People’s Hospital of Chenzhou, Youth Avenue No.8, Chenzhou, 423000, Hunan, China;2. Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Zhongshan Road No.222, Dalian, 116011, China;3. Department of Ophthalmology, Shenzhen People’s Hospital Affiliated to Jinan University, Dongmen North Road No. 1017, Shenzhen 518020, Guangdong, China;4. Department of Ophthalmology, Shenzhen Eye Hospital, Shenzhen Eye Institute, School of Optometry, Shenzhen University Department of Ophthalmology, Zetian Road No. 18, Shenzhen, 518040, Guangdong, China;1. Department of Ophthalmology, The First People’s Hospital of Jinzhou (Yangtze University Affiliated First People’s Hospital), Hubei, 434000, PR China;2. Department of Oncology, Jingzhou Central Hospital, The Second Clinical Medical College of Yangtze University, Hubei, 434020, PR China;3. Department of Ophthalmology, Xiangyang Central Hospital, Hubei, 441021, PR China |
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Abstract: | BackgroundRetinoblastoma (RB) is the most common primary intraocular malignancy in children. Accumulating evidences have clarified that microRNAs (miRNAs) modulated signaling molecules by acting as oncogenes or tumor-suppressor genes in RB. Thus, in our study, we aimed to investigate the function of miR-129-5p in RB cells through PI3K/AKT signaling pathway by targeting PAX6. Two RB cell lines, Y79 and WERI-Rb-1, were selected in our study, followed by transfection of miR-129-5p inhibitor or si-PAX6 to explore the regulatory role of miR-129-5p in RB cell proliferation, invasion and migration.Material and methodsDual-luciferase assay was used for the detection of targeting relationship between miR-129-5p and PAX6. Besides, western blot analysis was applied to detect expression of cell cycle-related factors (CDK2 and Cyclin E) and PI3K/AKT signaling pathway-related factors (p-AKT and AKT). Nude mice tumorigenesis experiment was used to evaluate the effect of miR-129a-5p on RB growth in vivo.ResultsmiR-129-5p was down-regulated in RB cell lines. miR-129-5p directly targeted the 3′-untranslated region of PAX6. Artificial down-regulation of miR-129-5p promoted cell proliferation, migration and invasion in RB cell lines Y79 and WERI-Rb-1, and promoted RB growth in vivo via PI3K/AKT signaling pathway, which could be reversed by transfection with silencing PAX6.ConclusionThis study provides evidences that RB progression was suppressed by overexpressed miR-129-5p via direct targeting of PAX6 through PI3K/AKT signaling pathway, which may provide a molecular basis for better treatment for RB. |
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Keywords: | Retinoblastoma miR-129-5p PAX6 PI3K/AKT signaling pathway Proliferation Invasion Migration |
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