miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3.

miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3.
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DOI:
10.1038/s41419-018-0738-z
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发表时间:
2018-06-07
影响因子:
9
通讯作者:
Guo W
Guo W
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang H;Yang K;Ren T;Huang Y;Tang X;Guo W

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异常表达的miRNAs在包括脊索瘤在内的多种癌症类型的发展中起着至关重要的作用。然而,其详细的分子机制尚不清楚,需要进一步阐明。在本研究中,通过miRNA阵列分析来筛选miRNAs,然后通过实时荧光定量PCR分析来证实。我们发现miR-16-5p在脊索瘤中的表达显著下调,而miR-16-5p的过表达抑制了脊索瘤细胞的增殖、侵袭和体内迁移,并与E-钙粘蛋白的表达上调以及N-钙粘蛋白和波形蛋白的表达下调有关。此外,Smad3被确定为miR-16-5p的靶标,并且Smad3在脊索瘤组织中高表达。进一步的研究表明,抑制Smad3在脊索瘤细胞中的作用与过表达miR-16-5p的作用相似。我们的研究结果表明miR-16-5p通过靶向Smad3在脊索瘤的进展中发挥肿瘤抑制作用,这可能为脊索瘤的治疗提供一种有前途的预后和治疗策略。
Aberrantly expressed miRNAs play a crucial role in the development of multiple cancer types, including chordoma. However, the detailed molecular mechanisms are unclear and need to be elucidated. In this study, miRNAs were screened by miRNA array analysis and then confirmed by real-time PCR analysis. We found that miR-16-5p was significantly downregulated in chordoma, and overexpression of miR-16-5p suppressed chordoma cell proliferation, invasion and migration in vitro and in vivo and correlated with the upregulated expression of E-cadherin and downregulated expression of N-cadherin and vimentin. Furthermore, Smad3 was identified as a target of miR-16-5p, and Smad3 was highly expressed in chordoma tissues. Further research showed that knockdown of Smad3 had an effect similar to that of overexpression of miR-16-5p in chordoma cells. Our findings demonstrate that miR-16-5p plays a tumor suppressor role in chordoma progression by targeting Smad3, which could provide a promising prognostic and therapeutic strategy for chordoma treatment.
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