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解析 microRNA 有助于阐明人类乳腺癌的生理学和功能,为治疗干预提供依据。

Dissecting miRNA facilitated physiology and function in human breast cancer for therapeutic intervention.

机构信息

Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.

Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.

出版信息

Semin Cancer Biol. 2021 Jul;72:46-64. doi: 10.1016/j.semcancer.2020.05.017. Epub 2020 Jun 1.

DOI:10.1016/j.semcancer.2020.05.017
PMID:32497683
Abstract

MicroRNAs (miRNAs) are key epigenomic regulators of biological processes in animals and plants. These small non coding RNAs form a complex networks that regulate cellular function and development. MiRNAs prevent translation by either inactivation or inducing degradation of mRNA, a major concern in post-transcriptional gene regulation. Aberrant regulation of gene expression by miRNAs is frequently observed in cancer. Overexpression of various 'oncomiRs' and silencing of tumor suppressor miRNAs are associated with various types of human cancers, although overall downregulation of miRNA expression is reported as a hallmark of cancer. Modulations of the total pool of cellular miRNA by alteration in genetic and epigenetic factors associated with the biogenesis of miRNA machinery. It also depends on the availability of cellular miRNAs from its store in the organelles which affect tumor development and cancer progression. Here, we have dissected the roles and pathways of various miRNAs during normal cellular and molecular functions as well as during breast cancer progression. Recent research works and prevailing views implicate that there are two major types of miRNAs; (i) intracellular miRNAs and (ii) extracellular miRNAs. Concept, that the functions of intracellular miRNAs are driven by cellular organelles in mammalian cells. Extracellular miRNAs function in cell-cell communication in extracellular spaces and distance cells through circulation. A detailed understanding of organelle driven miRNA function and the precise role of extracellular miRNAs, pre- and post-therapeutic implications of miRNAs in this scenario would open several avenues for further understanding of miRNA function and can be better exploited for the treatment of breast cancers.

摘要

微小 RNA(miRNAs)是动植物生物过程中关键的表观遗传调控因子。这些小的非编码 RNA 形成复杂的网络,调节细胞功能和发育。miRNAs 通过使 mRNA 失活或诱导其降解来阻止翻译,这是转录后基因调控的主要关注点。miRNA 对基因表达的异常调节在癌症中经常观察到。各种“致癌 miRNA”的过表达和肿瘤抑制 miRNA 的沉默与各种类型的人类癌症有关,尽管据报道 miRNA 表达的总体下调是癌症的一个标志。遗传和表观遗传因素的改变会调节细胞内 miRNA 的总池,这些因素与 miRNA 机制的生物发生有关。它还取决于细胞器中 miRNA 从其储存库中的可用性,这会影响肿瘤的发生和癌症的进展。在这里,我们剖析了各种 miRNA 在正常细胞和分子功能以及乳腺癌进展过程中的作用和途径。最近的研究工作和流行观点表明,存在两种主要类型的 miRNA:(i)细胞内 miRNA 和(ii)细胞外 miRNA。这一概念认为,哺乳动物细胞中细胞内 miRNA 的功能是由细胞器官驱动的。细胞外 miRNA 在细胞外空间的细胞间通讯和通过循环距离细胞中发挥作用。详细了解细胞器驱动的 miRNA 功能以及细胞外 miRNA 的精确作用,包括 miRNA 在这种情况下治疗前和治疗后的影响,将为进一步了解 miRNA 功能开辟几条途径,并可更好地用于治疗乳腺癌。

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