miR‑873 inhibits colorectal cancer cell proliferation by targeting TRAF5 and TAB1.

miR‑873 inhibits colorectal cancer cell proliferation by targeting TRAF5 and TAB1.
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MiR-873 通过靶向 TRAF5 和 TAB1 抑制结直肠癌细胞增殖

DOI:
10.3892/or.2018.6199
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发表时间:
2018-03
期刊:
影响因子:
4.2
通讯作者:
Zhang J
Zhang J
中科院分区:
医学3区
文献类型:
--
作者:
Gong H;Fang L;Li Y;Du J;Zhou B;Wang X;Zhou H;Gao L;Wang K;Zhang J

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MicroRNA-873(miR-873)在多种恶性肿瘤中表达异常,但miR-873在结直肠癌(CRC)中的生物学功能及其分子机制尚不清楚。在本研究中,我们发现miR-873在CRC细胞系和患者组织中的表达水平显著降低。统计学分析显示,miR-873的表达与CRC的疾病分期呈负相关。Kaplan-Meier生存分析显示,miR-873表达较低的CRC患者的总生存率较低。此外,miR-873的下调增强了CRC细胞的增殖,而miR-873的上调降低了这种增殖。此外,我们发现肿瘤坏死因子(TNF)受体相关因子5(TRAF 5)和TGF-β激活激酶1(MAP 3 K7)结合蛋白1(TAB 1)是miR-873在CRC细胞中的直接靶点。荧光素酶测定显示,miR-873的异位表达显著降低核因子κB(NF-κB)荧光素酶活性,而miR-873抑制剂的异位表达增强荧光素酶活性,表明miR-873的下调可激活NF-κB信号传导。因此,我们的发现确立了miR-873在抑制CRC进展中的肿瘤抑制作用,其可用作新的预后标记物和CRC的有效治疗靶点。
MicroRNA-873 (miR-873) has been reported to be dysregulated in a variety of malignancies, however, the biological function and underlying molecular mechanism of miR-873 in colorectal cancer (CRC) remain unclear. In the present study we found that the expression levels of miR-873 were markedly decreased in CRC cell lines and tissues from patients. Statistical analysis revealed that miR-873 expression was inversely correlated with the disease stage of CRC. Kaplan-Meier survival analysis revealed that patients with CRC with lower miR-873 expression had shorter overall survival rates. Additionally, downregulation of miR-873 enhanced the proliferation of CRC cells, while upregulation of miR-873 reduced this proliferation. Furthermore, we found that tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) and TGF-β activated kinase 1 (MAP3K7) binding protein 1 (TAB1) were direct targets of miR-873 in CRC cells. A luciferase assay revealed that ectopic expression of miR-873 significantly reduced nuclear factor κB (NF-κB) luciferase activity, while ectopic expression of miR-873 inhibitor enhanced luciferase activity, suggesting that downregulation of miR-873 can activate NF-κB signaling. Therefore, our findings established a tumor-suppressive role for miR-873 in the inhibition of CRC progression, which may be employed as a novel prognostic marker and as an effective therapeutic target for CRC.
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影响因子: 4
作者:
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发表时间: 2014-01-17
影响因子: 3.1
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发表时间: 2014-04
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