LncRNA CBR3-AS1 promotes osteosarcoma progression through the network of miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway

骨肉瘤 癌症研究 上皮-间质转换 PI3K/AKT/mTOR通路 下调和上调 生物 信号转导 细胞生物学 基因 遗传学
作者
Weitao Yao,Jingyu Hou,Guoqing Liu,Fangxing Wu,Qiang Yan,Liangyu Guo,Chuchu Wang
出处
期刊:Molecular Therapy - Oncolytics [Elsevier BV]
卷期号:25: 189-200 被引量:3
标识
DOI:10.1016/j.omto.2022.03.001
摘要

Long noncoding RNA (lncRNA) CBR3-AS1 (termed as CBR3-AS1) has been reported to be upregulated in several cancers including osteosarcoma. Its positive impact on the proliferation, migration, and invasion of osteosarcoma cells has been unveiled; nevertheless, whether it also affects the stemness and epithelial-mesenchymal transition (EMT) of osteosarcoma cells is unclear. The purpose for this study was to explore the effects of CBR3-AS1 on the stemness and EMT of osteosarcoma cells as well as its underlying mechanism. qRT-PCR and western blot were applied to detect target gene expression. Function assays were conducted to evaluate the effect of genes on the stemness and EMT of osteosarcoma cells. Mechanism assays were done to verify the association among different genes. In vivo assays were also performed. The obtained data showed that CBR3-AS1 demonstrated a high expression in osteosarcoma cells. CBR3-AS1 could promote stemness and EMT of osteosarcoma cells as well as osteosarcoma tumor growth. Mechanically, CBR3-AS1 sponged miR-140-5p and recruited DDX54 to upregulate NUCKS1, thus activating the mTOR signaling pathway. Furthermore, NUCKS1 could facilitate stemness and EMT of osteosarcoma cells. In summary, this study reveals that CBR3-AS1 exerts an oncogenic role in osteosarcoma through modulating the network of the miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway.

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