LncRNA NORAD promotes proliferation, migration and angiogenesis of hepatocellular carcinoma cells through targeting miR-211-5p/FOXD1/VEGF-A axis

• Published in: Microvascular research 2021-03, Vol.134, p.104120-104120, Article 104120
• Main Authors: Sun, Dong-Sheng, Guan, Cang-Hai, Wang, Wei-Na, Hu, Zeng-Tao, Zhao, Yu-Qiao, Jiang, Xing-Ming
• Format: Article
• Language: English
• Subjects: Angiogenesis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Movement; Cell Proliferation; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Hepatocellular carcinoma cells; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; MicroRNAs - genetics; MicroRNAs - metabolism; miR-211-5p; Neoplasm Invasiveness; Neovascularization, Physiologic; NORAD; Proliferation; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2020.104120

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death around the world. Despite improvement in the prevention and treatment of HCC, the clinical prognosis is still poor with increasing mortality. Non-coding RNAs play pivotal roles in HCC oncogenesis, but the detailed mechanism is poorly known. Therefore, the functions and interaction of lncRNA NORAD and miR-211-5p in HCC was investigated in this study. Quantitative real-time PCR method was used to analyze the expression of NORAD and miR-211-5p in clinical HCC tissues and cultured cell lines. Knockdown of NORAD and overexpression of miR-211-5p were then carried in HCC cells. Moreover, bioinformatics analysis and luciferase report assays were further employed to analyze the interaction between miR-211-5p and NORAD or FOXD1. Increased lncRNA NORAD and decreased miR-211-5p expression were first detected in HCC compared with the peritumorial area. Further studies showed that knockdown of NORAD or overexpression of miR-211-5p impaired the proliferation, migration and angiogenesis of HCC cells. Mechanistically, we found that NORAD functions as a sponge for miR-211-5p. Moreover, it was revealed that decreased miR-211-5p induced the expression of FOXD1 as well as its downstream target VEGF-A, thereby contributes to enhanced angiogenesis of HCC. Elevated NORAD works as a sponge for miR-211-5p in HCC, thus release the inhibition effect of the latter on its downstream target FOXD1 and VEGF-A, which finally promotes angiogenesis. These results provide new insights into the interaction between NORAD and miR-211-5p in HCC and their potential usage as targets for the development of novel therapeutics against HCC. •NORAD level is higher and miR-211-5p is lower in HCC tissue than that in peritumorial tissue.•Knockdown of NORAD or overexpression of miR-211-5p impairs the proliferation, migration and angiogenesis of HCC cells.•NORAD functions as a ceRNA of miR-211-5p.•MiR-211-5p exerts its function through direct regulating FOXD1/VEGF-A pathway.