MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism.

MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism.
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MicroRNA-217 可作为预后预测因子,并通过 AEG-1 依赖性机制抑制结直肠癌细胞增殖和侵袭

DOI:
10.1186/s12885-015-1438-z
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发表时间:
2015-05-28
期刊:
影响因子:
3.8
通讯作者:
Wang S
Wang S
中科院分区:
医学2区
文献类型:
--
作者:
Wang B;Shen ZL;Jiang KW;Zhao G;Wang CY;Yan YC;Yang Y;Zhang JZ;Shen C;Gao ZD;Ye YJ;Wang S

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最近的研究表明miR-217可能在肿瘤发生中发挥作用。然而,miR-217在结直肠癌(CRC)中的作用在很大程度上仍不清楚。采用定量逆转录聚合酶链式反应(qRT-PCR)检测50例结直肠癌组织及相应的非癌组织中miR-217和AEG-1的表达。分析miR-217的临床意义。建立了miR-217上调和AEG-1沉默的大肠癌细胞系,观察其对肿瘤生长的影响。双荧光素酶报告基因分析也被用来研究miR-217与AEG-1的相互作用。我们的数据显示,miR-217在50对结直肠癌组织中显著下调。MIR-217表达水平与肿瘤分化程度密切相关。此外,miR-217表达降低也与结直肠癌患者的总生存期缩短有关。MIR-217过表达通过促进细胞凋亡和G0/G1期阻滞,显著抑制了结直肠癌细胞的增殖、克隆形成和侵袭能力。有趣的是,异位miR-217表达降低了AEG-1的表达,并抑制了与AEG-1 3‘-非翻译区(UTR)相关的荧光素酶活性。AEG-1沉默导致的生物学行为改变与miR-217过表达相关的改变相似。最后,在裸鼠移植瘤模型中,miR-217过表达显著抑制了CRC细胞的生长。我们的研究结果表明,miR-217作为结直肠癌的预后标志物和潜在的治疗靶点具有相当大的价值。本文的在线版本(doi:10.1186/s12885-0151438-z)包含补充材料,授权用户可以使用。
Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3′-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC. The online version of this article (doi:10.1186/s12885-015-1438-z) contains supplementary material, which is available to authorized users.
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