Abstract
Tumor angiogenesis plays a critical role in the tumor progression. Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA) that acts as an oncogene in gliomas. We found that HULC, vascular endothelial growth factor (VEGF), and ESM-1 (endothelial cell specific molecule 1) expression and microvessel density were positively correlated with grade dependency in glioma patient tissues, and that HULC silencing suppressed angiogenesis by inhibiting glioma cells proliferation and invasion. This process induced anoikis and blocked the cell cycle at G1/S phase via the PI3K/Akt/mTOR signaling pathway, thus regulating the tumor-related genes involved in the above biological behavior in human glioma U87MG and U251 cells. However, these effects were reversed by ESM-1 overexpression, suggesting a mediating role of ESM-1 in the pro-angiogenesis effect of HULC. Our results define the mechanism of the pro-angiogenesis activity of HULC, which shows potential for application as a therapeutic target in glioma.
Highlights
The highly up-regulated in liver cancer (HULC) human long noncoding RNA is multifunctional and is implicated in various cellular processes, including cancer [1]
We studied the levels of HULC, ESM-1 and angiogenesis (CD34 and vascular endothelial growth factor (VEGF)) in the tissues of glioma patients
As others long noncoding RNA, HULC has been shown to act as an oncogene in human hepatic carcinoma, esophageal www.impactjournals.com/oncotarget cancer, osteosarcoma and pancreatic cancer [15]
Summary
The highly up-regulated in liver cancer (HULC) human long noncoding RNA is multifunctional and is implicated in various cellular processes, including cancer [1]. Up-regulation of HULC has been detected in many human malignancies, such as esophageal cancer, osteosarcoma, pancreatic cancer and hepatocellular carcinoma [2,3,4,5]. Tumor cells are plastic and can alter cell markers and functions to adapt to the microenvironment, including generating vascularization through vasculogenic mimicry (angiogenesis). Angiogenesis is accompanied by the inhibition of tumor apoptosis and the induction of invasion by pro-angiogenesis factors. Vascular endothelial growth factor-A (VEGF-A) is a pro-angiogenesis gene that is associated with tumor angiogenesis and tumor malignancy, and it induces tumor proliferation, migration invasion and survival
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