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癌症中 miRNA 生物发生调控的复杂性。

Complexity in regulating microRNA biogenesis in cancer.

机构信息

Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101.

Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101.

出版信息

Exp Biol Med (Maywood). 2020 Mar;245(5):395-401. doi: 10.1177/1535370220907314. Epub 2020 Feb 19.

Abstract

UNLABELLED

The discovery of microRNA (miRNA) significantly extends our knowledge on gene regulation and noncoding gene functions. MiRNAs are important post-transcriptional regulators involve in a wide range of biological functions and diseases, including cancer. MiRNAs are produced by a unique biogenesis pathway involving the two-step sequential nuclear and cytoplasmic RNase-dependent processing at post-transcriptional level. However, a specific (set) of miRNA(s) is (are) synthesized under certain circumstance or developmental/pathological stage to fine-tune the gene expression profile. In this minireview, we will discuss the mechanism of miRNA biogenesis in cancer, mainly focusing on how Drosha and Dicer, two critical molecules controlling miRNA biogenesis, are modulated and which factor contributes to the specificity of selected miRNA maturation.

IMPACT STATEMENT

The canonical maturation pathway of miRNAs is highly conserved, indicating the crucial roles of these mini-regulators in most cellular processes. Dysregulation of specific miRNAs or imbalance of miRNA abundance has been observed in cancers. Accumulating evidence has shown that the interplay between miRNA processing factors and regulatory proteins previously known as key players in cancer malignancy regulates the biogenesis of miRNAs, expression of target genes, and eventually the alteration of cellular phenotypes. This minireview summarizes the current findings in the modulation of miRNA biogenesis in cancer to advance the understanding of how noncoding RNA contributes to cancer development and malignancy.

摘要

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微小 RNA(miRNA)的发现极大地扩展了我们对基因调控和非编码基因功能的认识。miRNA 是重要的转录后调控因子,参与广泛的生物学功能和疾病,包括癌症。miRNA 是通过两步连续的核和细胞质 RNA 依赖性加工在转录后水平上产生的,涉及独特的生物发生途径。然而,在特定的情况下或发育/病理阶段,会合成特定的(一组)miRNA,以微调基因表达谱。在这篇简评中,我们将讨论癌症中 miRNA 生物发生的机制,主要集中在 Drosha 和 Dicer 这两个控制 miRNA 生物发生的关键分子如何被调节,以及哪些因素有助于选择 miRNA 成熟的特异性。

重要性声明

miRNA 的经典成熟途径高度保守,表明这些小型调节剂在大多数细胞过程中起着至关重要的作用。在癌症中观察到特定 miRNA 的失调或 miRNA 丰度的失衡。越来越多的证据表明,miRNA 加工因子与调节蛋白之间的相互作用,这些蛋白以前被认为是癌症恶性的关键参与者,调节了 miRNA 的生物发生、靶基因的表达,最终改变了细胞表型。这篇简评总结了癌症中 miRNA 生物发生的调节的最新发现,以促进对非编码 RNA 如何促进癌症发展和恶性的理解。

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