Chen Shiyi, Yang Mingjia, Chang Shimin
Department of Orthopaedic Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, People's Republic of China.
Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, Jiangsu Province 210096, People's Republic of China.
Cancer Manag Res. 2020 Oct 23;12:10521-10530. doi: 10.2147/CMAR.S272230. eCollection 2020.
The objective of this study was to detect the expression of the long noncoding RNA (lncRNA) colorectal cancer-associated lncRNA (CCAL) in osteosarcoma tissues and to investigate its role in angiogenesis and the potential molecular mechanisms associated with this effect in osteosarcoma.
CCAL expression in 40 osteosarcoma tissues and 40 noncancerous tissues was measured by qRT-PCR (quantitative real-time polymerase chain reaction). Tube formation assays were performed to explore the role of CCAL in angiogenesis in osteosarcoma. In addition, the regulatory interaction between CCAL, miR-29b, and ANGPTL4 was investigated via luciferase reporter assay and bioinformatics predictive analysis.
Compared with noncancerous tissues, the expression of CCAL was markedly upregulated in osteosarcoma tissues. Higher CCAL expression levels were closely related to shorter overall survival in patients with osteosarcoma. Additionally, functional analysis indicated that CCAL could facilitate tumour angiogenesis in vitro and in vivo in osteosarcoma. Mechanistically, CCAL upregulated ANGPTL4 expression in osteosarcoma cells, and ANGPTL4 mediated angiogenic induction by CCAL in osteosarcoma. Moreover, CCAL directly targeted miR-29b in osteosarcoma. More importantly, we demonstrated that CCAL upregulated the expression of ANGPTL4 by sponging miR-29b, which promoted angiogenesis in osteosarcoma.
Our results show that CCAL promotes angiogenesis by regulating the miR-29b/ANGPTL4 axis in osteosarcoma.
本研究旨在检测长链非编码RNA(lncRNA)结直肠癌相关lncRNA(CCAL)在骨肉瘤组织中的表达,并探讨其在骨肉瘤血管生成中的作用以及与该效应相关的潜在分子机制。
采用qRT-PCR(定量实时聚合酶链反应)检测40例骨肉瘤组织和40例癌旁组织中CCAL的表达。进行管腔形成试验以探讨CCAL在骨肉瘤血管生成中的作用。此外,通过荧光素酶报告基因试验和生物信息学预测分析研究CCAL、miR-29b和ANGPTL4之间的调控相互作用。
与癌旁组织相比,CCAL在骨肉瘤组织中的表达明显上调。CCAL表达水平较高与骨肉瘤患者较短的总生存期密切相关。此外,功能分析表明,CCAL在体外和体内均可促进骨肉瘤的肿瘤血管生成。机制上,CCAL上调骨肉瘤细胞中ANGPTL4的表达,且ANGPTL4介导CCAL在骨肉瘤中的血管生成诱导作用。此外,CCAL在骨肉瘤中直接靶向miR-29b。更重要的是,我们证明CCAL通过海绵化miR-29b上调ANGPTL4的表达,从而促进骨肉瘤中的血管生成。
我们的结果表明,CCAL通过调节骨肉瘤中的miR-29b/ANGPTL4轴促进血管生成。