HULC long noncoding RNA silencing suppresses angiogenesis by regulating ESM-1 via the PI3K/Akt/mTOR signaling pathway in human gliomas

// Yu Zhu 1, * , Xuebin Zhang 2, * , Lisha Qi 3, * , Ying Cai 4 , Ping Yang 1 , Geng Xuan 5 , Yuan Jiang 6 1 Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, China 2 Department of Pathology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, China 3 Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin, China 4 Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, China 5 College of Clinical Laboratory, Tianjin Medical University, Tianjin, China 6 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China * These authors contributed equally to this work Correspondence to: Yu Zhu, e-mail: zhuyutj@126.com Ping Yang, e-mail: tjhhhospitallab@126.com Yuan Jiang, e-mail: jiangyuan23@163.com Keywords: lncRNA, HULC, glioma, anoikis, proliferation Received: October 06, 2015 Accepted: January 23, 2016 Published: February 15, 2016 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.