Loss of miR-101 expression promotes Wnt/β-catenin signalling pathway activation and malignancy in colon cancer cells

被引:102
|
作者
Strillacci, Antonio [1 ]
Valerii, Maria Chiara [1 ,2 ]
Sansone, Pasquale [3 ,4 ]
Caggiano, Cinzia [1 ]
Sgromo, Annamaria [1 ]
Vittori, Laura [2 ]
Fiorentino, Michelangelo [5 ]
Poggioli, Gilberto [2 ]
Rizzello, Fernando [2 ]
Campieri, Massimo [2 ]
Spisni, Enzo [1 ]
机构
[1] Univ Bologna, Dept Biol, I-40126 Bologna, Italy
[2] St Orsola Malpighi Hosp, Dept Clin Med, Bologna, Italy
[3] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA
[4] St Orsola Malpighi Hosp, Ctr Appl Biomed Res CRBA, Bologna, Italy
[5] St Orsola Malpighi Hosp, Addarii Inst Oncol, Pathol Unit, Bologna, Italy
来源
JOURNAL OF PATHOLOGY | 2013年 / 229卷 / 03期
关键词
Colorectal cancer; MiR-101; ss-catenin; hypoxia; EMT; inflammation; EPITHELIAL-MESENCHYMAL TRANSITION; BETA-CATENIN; TRANSCRIPTIONAL ACTIVATION; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; TUMOR PROGRESSION; RNA INTERFERENCE; UP-REGULATION; LUNG-CANCER; STEM-CELLS;
D O I
10.1002/path.4097
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:379 / 389
页数:11
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