首页> 美国卫生研究院文献>International Journal of Clinical and Experimental Pathology >MicroRNA-126 is down-regulated in human esophageal squamous cell carcinoma and inhibits the proliferation and migration in EC109 cell via PI3K/AKT signaling pathway
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MicroRNA-126 is down-regulated in human esophageal squamous cell carcinoma and inhibits the proliferation and migration in EC109 cell via PI3K/AKT signaling pathway

机译:MicroRNA-126在人食管鳞状细胞癌中下调,并通过PI3K / AKT信号通路抑制EC109细胞的增殖和迁移

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摘要

MicroRNA-126 (miR-126) was found down-regulated in different types of cancer including esophageal squamous cell carcinoma (ESCC). However, the onco-genetic role of miR-126 in ESCC still remains unknown. In the present study, we found the relative expression of miR-126 in ESCC was significant decreased in ESCC tissues compared to adjacent normal tissues. Overexpression of miR-126 in EC109 cells resulted in significant decrease in cell proliferation, colon formation and migration. PI3K regulatory subunit p85 beta (PIK3R2), a member of PI3K/AKT signaling pathway was found upregulated in ESCC tissues and there is a negative relation between expression of PIK3R2 and miR-126. Restoration of miR-126 in EC109 cells induced a reduction in PIK3R2 protein levels, accompanied with a substantial reduction in phosphorylated AKT levels in EC109 cells, suggesting impairment in PI3K/AKT signaling pathway. The luciferase reporter assay confirmed that PIK3R2 was a direct target of miR-126. Furthermore, we also indicated overexpression of miR-126 suppresses G2/M transition in EC109 cells. Taken together, our study suggests that miR-126 functions as a potential tumor suppressor in ESCC progression via regulating PI3K/AKT signaling pathway partly by targeting PIK3R2, and targeting of miR-126 may provide a novel strategy for the diagnosis and treatment of ESCC.
机译:发现MicroRNA-126(miR-126)在不同类型的癌症(包括食管鳞状细胞癌(ESCC))中被下调。但是,miR-126在ESCC中的癌基因作用仍然未知。在本研究中,我们发现与邻近的正常组织相比,ESCC组织中miR-126在ESCC中的相对表达显着降低。 miR-126在EC109细胞中的过表达导致细胞增殖,结肠形成和迁移明显减少。在ESCC组织中发现PI3K / AKT信号通路成员PI3K调节亚基p85 beta(PIK3R2)被上调,并且PIK3R2和miR-126的表达呈负相关。 EC109细胞中miR-126的恢复诱导了PIK3R2蛋白水平的降低,并伴随着EC109细胞中磷酸化AKT水平的显着降低,表明PI3K / AKT信号通路受损。荧光素酶报告基因测定证实PIK3R2是miR-126的直接靶标。此外,我们还表明miR-126的过表达抑制EC109细胞中的G2 / M过渡。两者合计,我们的研究表明,miR-126通过部分靶向PIK3R2调节PI3K / AKT信号通路,在ESCC进展中起潜在的抑癌作用,而靶向miR-126可能为ESCC的诊断和治疗提供新的策略。

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