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首页> 外文期刊>Oncology Research >Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer
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Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

机译：肿瘤抑制microRNA-708靶向NOTCH1以抑制胃癌中细胞增殖和侵袭

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摘要

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.
机译：日益增长的证据表明，许多微小RNA（miRNA）可以参与胃癌发生的调节和进展。这种现象表明，胃癌相关的miRNA可以被鉴定为这种疾病的有效治疗靶标。最近据报道，MiRNA-708（miR-708）已经在几种类型的癌症中表达，并且有助于致癌和进展。然而，胃癌中MiR-708的表达水平，生物作用和潜在机制尚不清楚。在这里，我们发现miR-708在胃癌组织和细胞系中下调。下调的miR-708表达明显与淋巴结转移，侵入深度和Tnm阶段显着相关。进一步调查表明，MIR-708的异位表达禁止细胞增殖和胃癌侵袭。生物信息学分析表明，Notch1是miR-708的潜在目标。通过双荧光素酶报告量测定，逆转录定量聚合酶链反应，逆转录定量聚合酶链反应和Western印迹分析，进一步证实了在胃癌中的miR-708的直接靶基因。此外，在胃癌组织中的miR-708和Notch1 mRNA水平之间发现了逆关节。此外，恢复的Notch1表达救出了MiR-708过表达的胃癌细胞增殖和侵袭的抑制作用。我们的研究结果突出了miR-708在胃癌中的肿瘤抑制作用，并表明MIR-708可以作为胃癌治疗的新靶标。

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