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纠结于细枝末节:微小 RNA 和遗传变化定义胰腺癌。

Sweating the small stuff: microRNAs and genetic changes define pancreatic cancer.

机构信息

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Pancreas. 2013 Jul;42(5):740-59. doi: 10.1097/MPA.0b013e3182854ab0.

DOI:10.1097/MPA.0b013e3182854ab0
PMID:23774697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4086428/
Abstract

MicroRNAs (miRNAs) are 18- to 22-nucleotide-long, single-stranded, noncoding RNAs that regulate important biological processes including differentiation, proliferation, and response to cellular stressors such as hypoxia, nutrient depletion, and traversion of the cell cycle by controlling protein expression within the cell. Many investigators have profiled cancer tissue and serum miRNAs to identify potential therapeutic targets, understand the pathways involved in tumorigenesis, and identify diagnostic tumor signatures. In the setting of pancreatic cancer, obtaining pancreatic tissue is invasive and impractical for early diagnosis. Several groups have profiled miRNAs that are present in the blood as a means to diagnose tumor progression and predict prognosis/survival or drug resistance. Several miRNA signatures found in pancreatic tissue and the peripheral blood, as well as the pathways that are associated with pancreatic cancer, are reviewed here in detail. Three miRNA biomarkers (miR-21, miR-155, and miR-200) have been repetitively identified in both pancreatic cancer tissue and patients' blood. Those miRNAs regulate and are regulated by the central genetic and epigenetic changes observed in pancreatic cancer including p53, transforming growth factor β, p16(INK4A), BRCA1/2, and Kras. These miRNAs are involved in DNA repair, cell cycle, and cell invasion and also play important roles in promoting metastases.

摘要

微小 RNA(miRNA)是长约 18 到 22 个核苷酸的单链非编码 RNA,可通过调控细胞内蛋白质的表达,来调控分化、增殖以及对缺氧、营养耗竭和细胞周期转变等细胞应激的反应等重要的生物学过程。许多研究人员对癌症组织和血清 miRNA 进行了分析,以确定潜在的治疗靶点,了解肿瘤发生过程中涉及的途径,并鉴定诊断肿瘤的特征。在胰腺癌的情况下,获取胰腺组织是具有侵入性的,并且不适合早期诊断。一些研究小组对存在于血液中的 miRNA 进行了分析,作为诊断肿瘤进展、预测预后/生存或耐药性的一种手段。本文详细综述了在胰腺组织和外周血中发现的几种 miRNA 特征,以及与胰腺癌相关的途径。三种 miRNA 生物标志物(miR-21、miR-155 和 miR-200)已在胰腺癌组织和患者血液中被反复鉴定。这些 miRNA 调节并受胰腺癌中观察到的核心遗传和表观遗传变化的调控,包括 p53、转化生长因子β、p16(INK4A)、BRCA1/2 和 Kras。这些 miRNA 参与 DNA 修复、细胞周期和细胞侵袭,也在促进转移中发挥重要作用。

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