MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients.
MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients.
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DOI：
10.1038/bjc.2014.51
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发表时间：
2014-03-18
影响因子：
8.8
通讯作者：
Hoefler, G.
中科院分区：
文献类型：
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作者：
Pichler, M.;Ress, A. L.;Winter, E.;Stiegelbauer, V.;Karbiener, M.;Schwarzenbacher, D.;Scheideler, M.;Ivan, C.;Jahn, S. W.;Kiesslich, T.;Gerger, A.;Bauernhofer, T.;Calin, G. A.;Hoefler, G.
MicroRNAs(MiRNAs)调控结直肠癌(CRC)细胞的生物学特性，可能成为潜在的预后因素和治疗靶点。因此，在这项研究中，我们对结直肠癌细胞中与E-钙粘附素表达相关的miRNAs进行了全局分析，试图确定与CRC患者侵袭性临床病程相关的miRNAs。利用基因芯片技术分析了两种不同E-钙粘附素表达模式的大肠癌细胞系(Caco-2和HRT-18)1000多个人类miRNAs的丰度差异。作为差异表达最多的miRNAs之一，miR-200A在111名患者的队列中进行了预后评估，并在癌症基因组图谱数据集的217名患者中独立验证。为了进一步研究miR-200A在结直肠癌中的生物学作用，我们在体外对miR-200A进行了抑制和过表达，并探讨了其对细胞生长、细胞凋亡和上皮-间充质转化(EMT)相关基因表达的影响。原位杂交将miR-200A特异性定位于结直肠癌细胞。在这两个队列中，miR-200A低表达与生存不良相关(P<；0.05)。多变量COX回归分析表明，miR-200a低表达是影响肿瘤特异性生存的独立预后因素(HR=2.04，CI=1.28-3.25，P<；0.002)。体外对miR-200A功能的获得和丧失分析导致了EMT相关基因的显著差异和反向表达(P<；0.001)。在肿瘤干细胞丰富的球形生长条件下，miR-200A的低表达也被观察到(P<；0.05)。综上所述，我们的数据表明，miR-200A的低表达与结直肠癌患者的预后不良有关。MIR-200A对EMT具有调节作用，并与结直肠癌的肿瘤干细胞特性有关。
MicroRNAs (miRNAs) regulate the biological properties of colorectal cancer (CRC) cells and might serve as potential prognostic factors and therapeutic targets. In this study, we therefore globally profiled miRNAs associated with E-cadherin expression in CRC cells in an attempt to identify miRNAs that are associated with aggressive clinical course in CRC patients. Two CRC cell lines (Caco-2 and HRT-18) with different E-cadherin expression pattern were profiled for differences in abundance for more than 1000 human miRNAs using microarray technology. One of the most differentially expressed miRNAs, miR-200a was evaluated for its prognostic role in a cohort of 111 patients and independently validated in 217 patients of the Cancer Genome Atlas data set. To further characterise the biological role of miR-200a expression in CRC, in vitro miR-200a inhibition and overexpression were performed and the effects on cellular growth, apoptosis and epithelial–mesenchymal transition (EMT)-related gene expression were explored. In situ hybridisation specifically localised miR-200a in CRC cells. In both cohorts, a low miR-200a expression was associated with poor survival (P<0.05). Multivariate Cox regression analysis identified low levels of miR-200a expression as an independent prognostic factor with respect to cancer-specific survival (HR=2.04, CI=1.28–3.25, P<0.002). Gain and loss of function assays for miR-200a in vitro led to a significantly differential and converse expression of EMT-related genes (P<0.001.) A low expression of miR-200a was also observed in cancer stem cell-enriched spheroid growth conditions (P<0.05). In conclusion, our data suggest that low miR-200a expression is associated with poor prognosis in CRC patients. MiR-200a has a regulatory effect on EMT and is associated with cancer stem cell properties in CRC.
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DOI：
10.1158/1078-0432.ccr-11-1452
发表时间：
2011-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bartley AN;Yao H;Barkoh BA;Ivan C;Mishra BM;Rashid A;Calin GA;Luthra R;Hamilton SR
通讯作者：
Hamilton SR
影响因子：
11.2
作者：
Heitzer, Ellen;Auer, Martina;Speicher, Michael R.
通讯作者：
Speicher, Michael R.
DOI：
10.1097/coc.0b013e3181fe4444
发表时间：
2012-02-01
影响因子：
2.6
作者：
Chua, Terence C.;Liauw, Winston;Morris, David L.
通讯作者：
Morris, David L.
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
50.5
作者：
Van Cutsem, E.;Nordlinger, B.;Cervantes, A.
通讯作者：
Cervantes, A.