LncRNA SNHG12 promotes tumorigenesis and metastasis in osteosarcoma by upregulating Notch2 by sponging miR-195-5p

被引:127
|
作者
Zhou, Sheng [1 ]
Yu, Ling [1 ]
Xiong, Min [2 ]
Dai, Guo [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Orthoped, Wuhan 430060, Hubei, Peoples R China
[2] Hubei Univ Med, Affiliated Dongfeng Gen Hosp, Dept Orthoped, Shiyan 442008, Hubei, Peoples R China
关键词
LncRNA SNHG12; miR-195-5p; Notch2; Osteosarcoma; LONG NONCODING RNA; COMPETING ENDOGENOUS RNA; HUMAN PROSTATE-CANCER; CELL LUNG-CANCER; GASTRIC-CANCER; SIGNALING PATHWAY; HEPATOCELLULAR-CARCINOMA; GALLBLADDER CANCER; TUMOR PROGRESSION; PROLIFERATION;
D O I
10.1016/j.bbrc.2017.12.047
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteosarcoma is the most common primary malignant bone tumor and has a high fatality rate in children and adolescents. Recently, an increasing amount of evidence has demonstrated that lncRNAs have crucial roles in regulating biological characteristics in malignant tumors. Therefore, this research was carried out to uncover the biological function and the potential molecular mechanism of SNHG12 in osteosarcoma. In this study, we found that SNHG12 was significantly upregulated in both osteosarcoma tissues and cell lines and osteosarcoma patients with high levels of SNHG12 tended to have a poor prognosis. We evaluated the biological function of SNHG12 in 143B and U2OS cells and show that the downregulation of SNHG12 suppressed cell proliferation by blocking cell cycle progression at the GO/G1 phase and weakened cell invasion and migration abilities. Dual-luciferase reporter and RIP assays were conducted to confirm that SNHG12 functioned as a ceRNA, modulating the expression of Notch2 by sponging miR-1955p in osteosarcoma. We further demonstrate that Notch2 played a crucial role in activating the Notch signaling pathway. In conclusion, SNHG12 might serve as a valuable biomarker and prognosis factor in osteosarcoma patients. The SNHG12/miR-195-5p/Notch2-Notch signaling pathway axis might become a novel therapeutic for osteosarcoma. (C) 2017 Published by Elsevier Inc.
引用
收藏
页码:1822 / 1832
页数:11
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