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Int J Clin Exp Pathol 2013;6(11):2323-2332

Original Article
Suppressing the malignant phenotypes of glioma cells by lentiviral delivery of small
hairpin RNA targeting hypoxia-inducible factor-1α

Chang Gui Dong, William K K Wu, Su Yin Feng, Jun Yu, Jun Fei Shao, Gui Mei He

Institute of Molecular Ecology and Evolution, IAIR, East China Normal University, Shanghai 200062, PR China; Institute of Digestive Disease,
Department of Medicine & Therapeutics and LKS Institute of Health, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China;
Department of Neurosurgery, Wuxi NO.4 People’s Hospital, Affiliated to Jiangnan University, Wuxi 214062, PR China; Department of
Neurosurgery, Wuxi People’s Hospital of Nanjing Medical University, Wuxi 214023, China. Equal contributors.

Received September 1, 2013; Accepted October 3, 2013; Epub October 15, 2013; Published November 1, 2013

Abstract: Hypoxic microenvironment of solid tumors is known to shape malignant phenotypes of cancer cells through the dimeric transcription
factor hypoxia-inducible factor (HIF)-1. In the present study, the therapeutic effect of targeting α subunit of HIF-1 in glioma cells via lentiviral
delivery of small hairpin RNA (shRNA) was evaluated. Data from quantitative real-time PCR and immunohistochemistry demonstrated that HIF-
1α was progressively upregulated during the development of gliomas. Lentiviral shRNA targeting HIF-1α led to substantial loss of cell viability,
G0/G1-phase cell cycle arrest, apoptosis, and impairment of cell motility and invasiveness in human glioma U87MG cells. Xenograft
experiments in nude mice further showed that HIF-1α-shRNA inhibited tumor growth and caused persistent repression of HIF-1α and its target
genes, including VEGF, GLUT1 and MMP2, up to 25 days post-inoculation. Taken together, lentiviral delivery of shRNA is a promising
therapeutic approach for targeting HIF-1α in glioma. (IJCEP1309002).

Keywords: Hypoxia-inducible factor, glioma, short hairpin RNA, lentivirus

Address correspondence to: Jun F Shao, Department of Neurosurgery, Wuxi People’s Hospital of Nanjing Medical University, Wuxi, 214023,
PR China. Tel: 86-0510-82700778; E-mail: wxbrain1@163.com; Gui M He, Institute of Molecular Ecology and Evolution, IAIR, East China
Normal University, Shanghai 200062, China. Tel: 86-021-62235786; E-mail: gmhe@bio.ecnu.edu.cn