LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer

被引:250
作者
Zhang, Gang [1 ,2 ,3 ]
Li, Shuwei [2 ,3 ]
Lu, Jiafei [2 ]
Ge, Yuqiu [2 ,3 ]
Wang, Qiaoyan [2 ,3 ]
Ma, Gaoxiang [2 ,3 ]
Zhao, Qinghong [4 ]
Wu, Dongdong [4 ]
Gong, Weida [5 ]
Du, Mulong [2 ,3 ]
Chu, Haiyan [2 ,3 ]
Wang, Meilin [2 ,3 ]
Zhang, Aihua [3 ,6 ]
Zhang, Zhengdong [2 ,3 ]
机构
[1] Nanjing Med Univ, Childrens Hosp, Dept Neurol, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Dept Environm Genom,Sch Publ Hlth, 101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol,Dept Genet Toxicol, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp 2, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China
[5] Yixing Canc Hosp, Dept Gen Surg, Yixing, Peoples R China
[6] Guizhou Med Univ, Minist Educ, Key Lab Environm Pollut Monitoring & Dis Control, Guiyang 550025, Guizhou, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
lncRNA; MT1JP; Gastric cancer; ceRNA; Prognosis; LONG NONCODING RNAS; COMPETING ENDOGENOUS RNA; FBW7 UBIQUITIN LIGASE; TUMOR-SUPPRESSOR; TARGETING FBXW7; PROLIFERATION; EXPRESSION; PATHWAY; GROWTH; DIFFERENTIATION;
D O I
10.1186/s12943-018-0829-6
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
Background: Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. Methods: LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. Results: LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. Conclusion: MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.
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页数:11
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