miR-365 promotes cutaneous squamous cell carcinoma (CSCC) through targeting nuclear factor I/B (NFIB).

miR-365 promotes cutaneous squamous cell carcinoma (CSCC) through targeting nuclear factor I/B (NFIB).
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miR-365 通过靶向核因子 I/B (NFIB) 促进皮肤鳞状细胞癌 (CSCC)

DOI:
10.1371/journal.pone.0100620
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ding Z
Ding Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhou M;Zhou L;Zheng L;Guo L;Wang Y;Liu H;Ou C;Ding Z

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microRNA的异常表达在肿瘤的发生发展中起着重要作用。由于转录因子(TF)是信号级联的关键组成部分,因此微小RNA对特定TF的特异性靶向作用可能决定了微小RNA在不同癌症中的作用。在这项研究中,我们确定了核因子I/B(NFI B)作为miR-365的靶点之一,miR-365先前被证实为皮肤鳞状细胞癌(CSCC)中的致癌miR。NFIB的下调是CSCC细胞系和来自患者的肿瘤中的一般特征,其显示显著上调的miR-365表达水平。基于siRNA的NFIB敲低通过miR-365的异位表达模拟正常细胞的致癌转化,这表明NFIB的消耗对于miR-365发挥其促致癌功能是必需的。NFIB可能是miR-365靶向CSCC发展的功能屏障。进一步的研究还发现了NFIB和miR-365在CSCC发展中形成的保守反馈调节回路,其可能潜在地用作治疗靶点以改善临床CSCC治疗。
Aberrant expression of microRNAs plays vital roles in tumor development and progression. As transcription factors (TFs) are the critical components of signaling cascades, specific targeting effects of microRNAs to specific TFs may determine the role of microRNAs in different cancers. In this study, we identified Nuclear Factor I/B (NFIB) as one of the targets of miR-365 which was previously verified as an onco-miR in cutaneous squamous cell carcinoma (CSCC). Down-regulation of NFIB was a general feature in both CSCC cell lines and tumors from patients which show drastically up-regulated miR-365 expression levels. The siRNA-based knockdown of NFIB mimic the carcinogenic transformation of normal cells by ectopically expression of miR-365 which indicates depletion of NFIB is necessary for miR-365 to exert its pro-carcinogenic function. NFIB may represent a functional barrier targeted by miR-365 to the development of CSCC. Further studies also discovered a conserved feedback regulatory circuitry formed by NFIB and miR-365 in CSCC development which may be potentially utilized as therapeutic target to improve the clinical CSCC treatment.
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