title: Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells.
abstract: OBJECTIVE Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. METHODS Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. RESULTS The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133+glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. CONCLUSIONS The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, these findings indicate that H19 plays an important role in tumorigenicity and stemness of glioblastoma and thus could be a therapeutic target for treatment of glioblastoma in the future.
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Huzhou Central Hospital, Huzhou.
authors.forename: Yukui
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu.
authors.forename: Minghua
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu.
authors.forename: Xiande
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Huzhou Central Hospital, Huzhou.
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu.
authors.forename: Degang
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing; and.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Suzhou University, Suzhou, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu.
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding
keywords: FBS = fetal bovine serum; H19; HCC = hepatocellular carcinoma; HUVEC = human umbilical vein endothelial cell; RT-qPCR = real-time quantitative reverse transcription polymerase chain reaction; SD = standard deviation; angiogenesis; glioblastoma; invasion; lncRNA = long noncoding RNA; long noncoding RNA; mouse; ncRNA = noncoding RNA; oncology; stemness