Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer.
Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer.
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DOI：
10.1186/1471-2407-9-374
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发表时间：
2009-10-20
期刊：
影响因子：
3.8
通讯作者：
Raponi M
中科院分区：
文献类型：
--
作者：
Arndt GM;Dossey L;Cullen LM;Lai A;Druker R;Eisbacher M;Zhang C;Tran N;Fan H;Retzlaff K;Bittner A;Raponi M
MicroRNA（MiRNA）是一类短的非编码RNA，通过多种机制调控蛋白质的表达。它们的表达改变已被证明与各种癌症有关。本研究的目的是分析miRNA在结直肠癌（CRC）中的表达，并分析特定miRNA在CRC细胞中的功能。MirVana miRNA Bioarrays用于确定8个CRC细胞系模型、45个不同阶段的人类CRC样本和4个匹配的正常结肠组织样本中的miRNA表达谱。用miR-143或miR-145表达载体稳定转导SW 620 CRC细胞，并在体外分析细胞增殖、细胞分化和锚定非依赖性生长。使用基因集富集分析鉴定与差异表达的miRNA相关的信号通路。临床CRC样本的表达分析鉴定了37个在CRC和正常组织之间差异表达的miRNA。此外，这些miRNA中的一些与CRC肿瘤进展相关，包括miR-133 a的丢失和miR-224的获得。我们在细胞系模型和临床样本中鉴定了11种在正常结肠和CRC之间差异表达的常见miRNA。体外功能研究表明，miR-143和miR-145似乎以相反的方式发挥作用，抑制或增加转移性CRC模型中的细胞增殖。miR-143和miR-145靶向的途径没有显示出显著的重叠。此外，转移性与非转移性等基因细胞系的基因表达分析表明，参与细胞周期和神经调节蛋白途径的miR-145靶标在转移背景下显著下调。在CRC的不同阶段表现出改变表达的miRNA可以成为CRC治疗的靶点，并进一步开发为潜在的诊断和预后分析物。在CRC中共表达的miRNAs共同靶向的已鉴定的生物学过程和信号通路为理解miRNAs在癌症中的功能作用提供了基础。
MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis. The expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context. MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in CRC provide a basis for understanding the functional role of miRNAs in cancer.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
37.3
作者：
Lanza G;Ferracin M;Gafà R;Veronese A;Spizzo R;Pichiorri F;Liu CG;Calin GA;Croce CM;Negrini M
通讯作者：
Negrini M
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
37.3
作者：
Bandrés E;Cubedo E;Agirre X;Malumbres R;Zárate R;Ramirez N;Abajo A;Navarro A;Moreno I;Monzó M;García-Foncillas J
通讯作者：
García-Foncillas J