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Dietary IVIetliyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis

机译:膳食伊维尔缺乏症,MicroRNA表达和肝癌的易感性

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摘要

MicroRNAs (miRNAs) are small 21-25 nucleotide-long non-coding RNAs that have emerged as key negative post-transcriptional regulators of gene expression [1, 2], Currently there are more than 700 mammalian miRNAs that can potentially target up to one-third of protein-coding human genes [1] involved in diverse physiological and pathological processes, including cancer [3, 4]. Indeed, aberrant levels of miRNAs have been reported in all major human malignancies [5,6]. In tumors, altered expression of miRNAs has been demonstrated to inhibit tumor suppressor genes or inappropriately activate oncogenes and has been associated with every aspect of tumor biology, including tumor progression, invasiveness, metastasis, and acquisition of resistance by malignantcells to chemotherapeutic agents [3, 4, 7, 8]. These observations lead to the suggestion that aberrant expression of miRNAs may contribute to tumorigenesis [9]. However, most of the tumor-miRNA-related studies are based on expression analysis of miRNAsin tumors in comparison with corresponding adjacent normal tissues [4-6]. The altered expression of any given miRNA in neoplastic cells is not sufficient to address conclusively the role of these changes in tumorigenesis [10]. Additionally, despite the established biological significance of miRNA dysregulation in neoplastic cells, there is a lack of knowledge on the role of miRNAs during early stages of tumor development, especially if variations in the expression of specific miRNAs are associated withdifferences in the susceptibility to tumorigenesis.
机译:microRNAs(miRNA)是小21-25个核苷酸长的非编码RNA,它被出现为基因表达的关键阴性后转录调节剂[1,2],目前有超过700名哺乳动物miRNA,可以潜在地瞄准一个 - 蛋白质编码的人类基因[1]参与不同的生理和病理过程,包括癌症[3,4]。实际上,所有主要人类恶性肿瘤都报告了异常水平的miRNA [5,6]。在肿瘤中,已经证明了MiRNA的改变表达以抑制肿瘤抑制基因或不恰当的激活癌基因,并且已经与肿瘤生物学的各个方面有关,包括肿瘤进展,侵袭性,转移和通过恶性细胞到化学治疗剂的耐药性[3, 4,7,8]。这些观察结果导致麦克麻类异常表达可能有助于肿瘤发生的建议[9]。然而,大多数肿瘤 - miRNA相关的研究基于与相应的相邻正常组织相应的mirnasin肿瘤的表达分析[4-6]。肿瘤细胞中任何给定的miRNA的改变表达不足以解决这些变化在肿瘤发生中的作用[10]。此外,尽管肿瘤细胞中miRNA失衡的既定生物学意义,但缺乏关于miRNA在肿瘤发育早期阶段的作用的知识,特别是如果特定miRNA表达的变化与肿瘤发生的易感性相关。

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