Long noncoding RNA NORAD regulates cancer cell proliferation and migration in human osteosarcoma by endogenously competing with miR‐199a‐3p
Autor: | Zhitao You, Jilong Zou, Xuming Wang, Jiabing Sun, Peng Zhang, Hongjun Chen, Zhiyuan Lu |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Clinical Biochemistry Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Gentamicin protection assay Cell Movement Cell Line Tumor microRNA Genetics medicine Humans Molecular Biology Cell Proliferation Osteosarcoma Reporter gene Cell Biology Transfection medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research RNA Long Noncoding |
Zdroj: | IUBMB Life. 71:1482-1491 |
ISSN: | 1521-6551 1521-6543 |
DOI: | 10.1002/iub.2064 |
Popis: | In this study, we evaluated the expressions and functions of a long noncoding RNA (lncRNA), Noncoding RNA activated by DNA damage (NORAD) in human osteosarcoma. NORAD expressions were evaluated by qRT-PCR in in vitro osteosarcoma cell lines and in vivo clinical specimens. SiRNA-induced NORAD downregulation was conducted in Saos-2 and 143B cells, and the functional effects of NORAD downregulation on osteosarcoma cells were evaluated by CCK-8 proliferation assay, 24-well transwell invasion assay and in vivo tumor explant assay, respectively. The possibility of NORAD endogenously competing microRNA target, hsa-miR-199a-3p was examined by dual-luciferase reporter assay and qRT-PCR. Then, hsa-miR-199a-3p was downregulated in NORAD-inhibited osteosarcoma cells to examine its role in regulating NORAD inhibition induced cancer suppression in osteosarcoma cells. NORAD was found to be significantly overexpressed in both osteosarcoma cells and osteosarcoma tumors. In Saos-2 and 143B cells transfected with NORAD-specific siRNA, their proliferation, invasion, and in vivo explant growth were all markedly suppressed. Hsa-miR-199a-3p was confirmed to be the competing target of NORAD. Its downregulation in Saos-2 and 143B cells inversely augment proliferation and invasion that were initially suppressed by NORAD-downregulation. The results of our study show that NORAD plays an important role in regulating cancer cell functions of osteosarcoma, possibly through endogenously competing with hsa-miR-199a-3p. |
Databáze: | OpenAIRE |
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