Loss of miR-101 expression promotes Wnt/β-catenin signalling pathway activation and malignancy in colon cancer cells
Loss of miR-101 expression promotes Wnt/β-catenin signalling pathway activation and malignancy in colon cancer cells
复制标题
DOI：
10.1002/path.4097
复制
发表时间：
2013-02-01
影响因子：
7.3
通讯作者：
Spisni, Enzo
中科院分区：
文献类型：
--
作者：
Strillacci, Antonio;Valerii, Maria Chiara;Spisni, Enzo
结直肠癌（CRC）是西方国家癌症相关死亡的第二大原因。尽管几种 microRNA (oncomiR) 的异常表达与 CRC 进展相关，但这种现象的分子机制仍在研究中。在这里，我们表明，根据肿瘤分级，miR-101 表达在 CRC 标本中存在差异性受损。 miR-101 重新表达可抑制 miR-101 水平低的 CRC 细胞的 3D 细胞生长、缺氧存活和侵袭潜力。此外，我们还提供了 miR-101 表达与重要 CRC 促恶性特征（例如炎症、Wnt/β-catenin 信号通路激活和上皮间质转化 (EMT)）之间双向调节机制的分子证据。然后，我们提出上调的 miR-101 可能在 CRC 中发挥肿瘤抑制因子的作用，并且其药理学恢复可能会阻碍 CRC 在体内的侵袭行为。 MiR-101 表达也可能代表结直肠癌诊断和预后的癌症生物标志物。版权所有 (C) 2012 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/beta-catenin signalling pathway and epithelialmesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.