Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways

Wei-Ming Fu; Ying-Fei Lu; Bao-Guang Hu; Wei-Cheng Liang; Xiao Zhu; Hai-di Yang; Gang Li; Jin-Fang Zhang

doi:10.18632/oncotarget.6731

Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways

Oncotarget. 2016 Jan 26;7(4):4712-23. doi: 10.18632/oncotarget.6731.

Authors

Wei-Ming Fu¹, Ying-Fei Lu^{1

2}, Bao-Guang Hu³, Wei-Cheng Liang⁴, Xiao Zhu⁵, Hai-di Yang⁶, Gang Li^{2

7}, Jin-Fang Zhang^{8

2

7}

Affiliations

¹ Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, P.R. China.
² Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China.
³ Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
⁴ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, P. R. China.
⁵ Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Guangdong Medical College, Dong guan, 523808, P.R. China.
⁶ Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
⁷ Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, P.R. China.
⁸ School of Medicine, South China University of Technology, Guangzhou 511458, P.R. China.

Abstract

Nasopharyngeal carcinoma (NPC), as a unique head and neck cancer type, is particularly prevalent in certain geographic areas such as eastern Asia. Until now, the therapeutic options have been restricted mainly to radiotherapy or chemotherapy. However, the clinical treatment effect remains unsatisfactory even if the combined radio-chemotherapies. Therefore, it is urgently needed to develop effective novel therapies against NPC. In this study, we discovered that lncRNA Hotair was extremely abundant in NPC cells and clinical NPC samples. Further studies showed that Hotair knockdown significantly attenuated both in vitro and in vivo tumor cell growth and angiogenesis. Our study also demonstrated that Hotair promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as through GRP78-mediated upregulation of VEGFA and Ang2 expression. Therefore, Hotair may serve as a promising diagnostic marker and therapeutic target for NPC patients.

Keywords: GRP78; angiogenesis; hotair; nasopharyngeal carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Biomarkers, Tumor / genetics*
Blotting, Western
Carcinoma
Cell Proliferation
Cells, Cultured
Endoplasmic Reticulum Chaperone BiP
Endothelium, Vascular / cytology
Endothelium, Vascular / metabolism
Female
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic*
HSP70 Heat-Shock Proteins / metabolism*
Humans
Immunoenzyme Techniques
Mice
Mice, Nude
Mitochondrial Proteins / metabolism*
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / blood supply*
Nasopharyngeal Neoplasms / genetics
Nasopharyngeal Neoplasms / metabolism
Nasopharyngeal Neoplasms / pathology
Neoplasm Staging
Neovascularization, Pathologic / genetics*
Prognosis
Promoter Regions, Genetic / genetics
RNA, Long Noncoding / genetics*
RNA, Small Interfering / genetics
Signal Transduction*
Vascular Endothelial Growth Factor A / antagonists & inhibitors
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
Xenograft Model Antitumor Assays

Substances

Biomarkers, Tumor
Endoplasmic Reticulum Chaperone BiP
HOTAIR long untranslated RNA, human
HSP70 Heat-Shock Proteins
HSPA5 protein, human
HSPA9 protein, human
Hspa5 protein, mouse
Mitochondrial Proteins
RNA, Long Noncoding
RNA, Small Interfering
VEGFA protein, human
Vascular Endothelial Growth Factor A