Guanghua Yang1, Chen Zeng1, Yang Liu2, Dongliang Li1, Juanjuan Cui1. 1. First Department of Oncology, Zhumadian Central Hospital Zhumadian, Henan, China. 2. Department of Pediatric Oncology, Zhumadian Central Hospital Zhumadian, Henan, China.
Abstract
BACKGROUND: ZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been studied in detail. This study aimed to determine the role of ZNRD1-AS1 in retinoblastoma. METHODS: Differentially expressed genes in retinoblastoma downloaded from GEO database were identified by Limma package, and the expression and cell location of ZNRD1-AS1 were detected by real-time quantitative PCR (RT-qPCR). The relationships between miR-128-3p and two genes (ZNRD1-AS1 and BMI1) were analyzed by bioinformatics and dual-luciferase assay. After manipulating the expressions of ZNRD1-AS1, miR-128-3p and BMI1, cell viability, tube length, migration, invasion and the protein expressions (PCNA, E-Cadherin, N-Cadherin) of retinoblastoma cells were determined by cell counting kit-8 (CCK-8), tube formation, transwell and Western blot assays, respectively. Subcutaneous transplantation tumor assay, immunohistochemistry, and RT-qPCR were applied to verify the functions of the target gene in vivo. RESULTS: ZNRD1-AS1 was up-regulated in the cytoplasm of retinoblastoma and regulated BMI1 via sponging miR-128-3p. ZNRD1-AS1 knockdown alleviated the malignant phenotype (viability, tube length, migration and invasion) of retinoblastoma cells, reduced tumor volume and weight, and inhibited BMI1 and CD34 expressions. Different from miR-128-3p mimic, miR-128-3p inhibitor promoted malignant phenotype of retinoblastoma cells, and partially reversed the inhibitory effect of siZNRD1-AS1. MiR-128-3p mimic down-regulated BMI1, PNCA, N-Cadherin expressions, and up-regulated p16 and E-Cadherin expressions. The regulatory effect of miR-128-3p was partially reversed by BMI1. CONCLUSION: ZNRD1-AS1, acting as a "sponge" of miR-128-3p, up-regulates BMI1, thereby promoting the progression of retinoblastoma. AJTR
BACKGROUND:ZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been studied in detail. This study aimed to determine the role of ZNRD1-AS1 in retinoblastoma. METHODS: Differentially expressed genes in retinoblastoma downloaded from GEO database were identified by Limma package, and the expression and cell location of ZNRD1-AS1 were detected by real-time quantitative PCR (RT-qPCR). The relationships between miR-128-3p and two genes (ZNRD1-AS1 and BMI1) were analyzed by bioinformatics and dual-luciferase assay. After manipulating the expressions of ZNRD1-AS1, miR-128-3p and BMI1, cell viability, tube length, migration, invasion and the protein expressions (PCNA, E-Cadherin, N-Cadherin) of retinoblastoma cells were determined by cell counting kit-8 (CCK-8), tube formation, transwell and Western blot assays, respectively. Subcutaneous transplantation tumor assay, immunohistochemistry, and RT-qPCR were applied to verify the functions of the target gene in vivo. RESULTS:ZNRD1-AS1 was up-regulated in the cytoplasm of retinoblastoma and regulated BMI1 via sponging miR-128-3p. ZNRD1-AS1 knockdown alleviated the malignant phenotype (viability, tube length, migration and invasion) of retinoblastoma cells, reduced tumor volume and weight, and inhibited BMI1 and CD34 expressions. Different from miR-128-3p mimic, miR-128-3p inhibitor promoted malignant phenotype of retinoblastoma cells, and partially reversed the inhibitory effect of siZNRD1-AS1. MiR-128-3p mimic down-regulated BMI1, PNCA, N-Cadherin expressions, and up-regulated p16 and E-Cadherin expressions. The regulatory effect of miR-128-3p was partially reversed by BMI1. CONCLUSION:ZNRD1-AS1, acting as a "sponge" of miR-128-3p, up-regulates BMI1, thereby promoting the progression of retinoblastoma. AJTR
Authors: Johannes Kettunen; Taru Tukiainen; Antti-Pekka Sarin; Alfredo Ortega-Alonso; Emmi Tikkanen; Leo-Pekka Lyytikäinen; Antti J Kangas; Pasi Soininen; Peter Würtz; Kaisa Silander; Danielle M Dick; Richard J Rose; Markku J Savolainen; Jorma Viikari; Mika Kähönen; Terho Lehtimäki; Kirsi H Pietiläinen; Michael Inouye; Mark I McCarthy; Antti Jula; Johan Eriksson; Olli T Raitakari; Veikko Salomaa; Jaakko Kaprio; Marjo-Riitta Järvelin; Leena Peltonen; Markus Perola; Nelson B Freimer; Mika Ala-Korpela; Aarno Palotie; Samuli Ripatti Journal: Nat Genet Date: 2012-01-29 Impact factor: 38.330
Authors: Helen Dimaras; Timothy W Corson; David Cobrinik; Abby White; Junyang Zhao; Francis L Munier; David H Abramson; Carol L Shields; Guillermo L Chantada; Festus Njuguna; Brenda L Gallie Journal: Nat Rev Dis Primers Date: 2015-08-27 Impact factor: 52.329