长链非编码 RNA MT1JP 通过竞争性结合 miR-92a-3p 在胃癌中作为 ceRNA 调节 FBXW7。
LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer.
机构信息
Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Department of Environmental Genomics, School of Public Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
出版信息
Mol Cancer. 2018 May 2;17(1):87. doi: 10.1186/s12943-018-0829-6.
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.
背景
越来越多的证据表明，长链非编码 RNA（lncRNA）的失调功能与胃癌（GC）有关。然而，差异表达的 lncRNA 在 GC 中的作用尚未完全阐明。
方法
通过 lncRNA 微阵列在 5 对正常和 GC 组织中确定 lncRNA 表达谱，并用定量实时 PCR（qRT-PCR）在另外 75 对组织中进一步验证。通过过表达 lncRNA MT1JP 来评估 MT1JP 在体外和体内的作用。通过荧光素酶报告基因测定、Western blot 和挽救实验来证明其生物学功能。
结果
lncRNA MT1JP 在 GC 组织中明显低于相邻正常组织，且较高的 MT1JP 与淋巴结转移和晚期显著相关。此外，MT1JP 表达较高的 GC 患者的生存情况较好。功能上，lncRNA MT1JP 的过表达抑制了细胞的增殖、迁移和侵袭，促进了细胞凋亡，在体内抑制了肿瘤的生长和转移。功能分析表明，lncRNA MT1JP 通过竞争性结合 miR-92a-3p 来调节 FBXW7 的表达。miR-92a-3p 和下调的 FBXW7 通过挽救分析逆转了 lncRNA MT1JP 引起的细胞表型。
结论
GC 中下调的 lncRNA MT1JP 与恶性肿瘤表型和 GC 患者的生存有关。MT1JP 通过作为竞争性内源性 RNA（ceRNA）来竞争性结合 miR-92a-3p 并调节 FBXW7 的表达，从而调节 GC 的进展。我们的研究为 lncRNA MT1JP 的转录后调控机制提供了新的见解，并表明 MT1JP 可能作为 GC 的潜在治疗靶点和预后生物标志物。
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