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

LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer.
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LncRNA MT1JP 在胃癌中作为 ceRNA 通过与 miR-92a-3p 竞争性结合来调节 FBXW7

DOI:
10.1186/s12943-018-0829-6
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发表时间:
2018-05-02
期刊:
影响因子:
37.3
通讯作者:
Zhang Z
Zhang Z
中科院分区:
医学1区
文献类型:
--
作者:
Zhang G;Li S;Lu J;Ge Y;Wang Q;Ma G;Zhao Q;Wu D;Gong W;Du M;Chu H;Wang M;Zhang A;Zhang Z

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越来越多的证据表明,长非编码RNA(Long Non-Coding RNAs,LncRNAs)功能失调与胃癌的发生密切相关。然而,差异表达的lncRNAs在GC中的作用还没有完全解释。用LncRNA微阵列检测5对正常组织和GC组织中LncRNA的表达谱,并用实时定量聚合酶链式反应(qRT-PCR)进一步验证75对组织中LncRNA的表达谱。用过表达的方法检测MT1JP的体外和体内作用。通过荧光素酶报告实验、Western blotting和救援实验对其生物学功能进行了验证。LncRNA MT1JP在胃癌组织中的表达明显低于癌旁正常组织,而MT1JP的升高与胃癌的淋巴结转移和分期密切相关。此外,MT1JP高表达的胃癌患者的生存状况良好。在功能上,过表达LncRNA MT1JP在体外抑制细胞的增殖、迁移、侵袭,促进细胞的凋亡,在体内抑制肿瘤的生长和转移。功能分析表明,lncRNA MT1JP通过与miR-92a-3p竞争性结合来调控FBXW7的表达。救援分析显示,MIR-92a-3p和下调的FBXW7逆转了由IncRNA MT1JP引起的细胞表型。MT1JP是一种在胃癌中表达下调的lncRNA,与胃癌的恶性表型和生存期有关。MT1JP通过竞争内源性RNA(CerNA)与miR-92a-3p竞争结合,调节FBXW7的表达,从而调控GC的进展。我们的研究为我们对lncRNA MT1JP转录后调控机制提供了新的见解,并提示MT1JP可能作为一种潜在的胃癌治疗靶点和预后生物标志物。
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. 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. 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. 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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