title: microRNA response element‑regulated TIKI2 expression suppresses the tumorigencity of malignant gliomas.
abstract: Glioma is the most common brain malignancy and has a very poor prognosis. The current treatment options have a minimal benefit on prolonging patient survival time. Accumulating data have shown that the WNT signaling pathway has a critical function in the progression and invasion of glioma. Thus, targeting WNT signaling appears to be an effective anti‑glioma strategy. TIKI2 was recently found to suppress the activation of the WNT signaling pathway by post‑translationally modifying secreted WNT proteins. The implication of TIKI2 aberrance in cancers and its potential therapeutic effect, however, has not been studied. In the present study, a glioma‑specific adenoviral vector was constructed, which was regulated by response elements of miR‑124, to express TIKI2 in glioma cells (Ad‑TIKI2‑124). Ad‑TIKI2‑124 was found to potently suppress the activation of WNT signaling in glioma cells. This inhibitory effect on the WNT signaling pathway lead to the reduction in proliferation, colony formation ability and invasion of glioma cell lines. In addition, animal experiments confirmed that the expression of the Ad‑TIKI2‑124 construct could compromise the tumorigenicity of glioma cells in vivo. Furthermore, this glioma‑selective TIKI2 expression protected normal cells from toxicity. In conclusion, the present study demonstrated that adenovirus‑mediated TIKI2 therapy may be used for glioma treatment and therefore warrants further clinical studies.
authors: Department of Brain Surgery, Xinxiang Center Hospital, Xinxiang, Henan 453000, P.R. China.
authors: Chuan-You
authors: CY
authors: Li
authors: Department of Brain Surgery, Xinxiang Center Hospital, Xinxiang, Henan 453000, P.R. China.
authors: Hong-Yun
authors: HY
authors: Zhang
authors: Department of Neurosurgery, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors: Yi-Lu
authors: YL
authors: Gao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D020218:Response Elements; D014162:Transfection; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin; D008666:Metalloendopeptidases; C000595448:TRABD2B protein, human