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MicroRNA-210 Promotes Proliferation and Invasion of Peripheral Nerve Sheath Tumor Cells Targeting EFNA3

机译:MicroRNA-210促进针对EFNA3的周围神经鞘肿瘤细胞的增殖和侵袭

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MicroRNA (miR) plays an important role in tumorigenesis including malignant peripheral nerve sheath tumor (MPNST). miR-210 downregulation is frequently observed in a variety of tumors. In this study, miR-210 was identified as downregulated in MPNST cells, and its potential target ephrin-A3 (EFNA3) was upregulated in them compared with neurofibroma cells using quantitative real-time (qRT)-PCR. Luciferase reporter assay further demonstrates that EFNA3 is a target of miR-210. Then it is confirmed that miR-210 can regulate EFNA3 mRNA and protein expression in MPNST ST88-14 (NF1 wild-type) and sNF96.2 (NF1 mutant type) cell lines. The functions of miR-210 in MPNST cells were investigated, and the results showed that overex-pression of miR-210 increased cellular viability, colony formation, S phase percentage, and invasiveness of MPNST cells. Inversely, inhibition of miR-210 expression induced suppression of proliferation and invasion of MPNST cells. These results suggest that miR-210-mediated EFNA3 promotion of proliferation and invasion of MPNST cells plays an important role in MPNST tumorigenesis and progression. miR-210 and EFNA3 may be candidate novel therapeutic targets for MPNST.
机译:MicroRNA(miR)在包括恶性周围神经鞘瘤(MPNST)在内的肿瘤发生中起着重要作用。在多种肿瘤中经常观察到miR-210下调。在这项研究中,miR-210被鉴定为在MPNST细胞中被下调,与使用定量实时(qRT)-PCR的神经纤维瘤细胞相比,其潜在的靶标ephrin-A3(EFNA3)在它们中被上调。荧光素酶报告基因测定进一步证明EFNA3是miR-210的靶标。然后证实,miR-210可以调节MPNST ST88-14(NF1野生型)和sNF96.2(NF1突变型)细胞系中的EFNA3 mRNA和蛋白表达。研究了miR-210在MPNST细胞中的功能,结果表明miR-210的过表达增加了MPNST细胞的细胞活力,集落形成,S期百分数和侵袭性。相反,抑制miR-210表达可抑制MPNST细胞的增殖和侵袭。这些结果表明,miR-210介导的EFNA3促进MPNST细胞增殖和侵袭在MPNST肿瘤发生和发展中起重要作用。 miR-210和EFNA3可能是MPNST的候选新型治疗靶标。

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