LncRNA CCAL Promotes Angiogenesis Through Regulating the MiR-29b/ANGPTL4 Axis in Osteosarcoma

Cancer Manag Res. 2020 Oct 23:12:10521-10530. doi: 10.2147/CMAR.S272230. eCollection 2020.

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: Our results show that CCAL promotes angiogenesis by regulating the miR-29b/ANGPTL4 axis in osteosarcoma.

Keywords: ANGPTL4; angiogenesis; lncRNA CCAL; miR-29b; osteosarcoma.