MicroRNA expression profiles in human colorectal cancers with liver metastases

MicroRNA expression profiles in human colorectal cancers with liver metastases
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DOI:
10.3892/or.2010.1112
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发表时间:
2011-03-01
期刊:
影响因子:
4.2
通讯作者:
Shen, Xaoying
Shen, Xaoying
中科院分区:
医学3区
文献类型:
--
作者:
Lin, Maosong;Chen, Weichang;Shen, Xaoying

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目前,由于基因表达的复杂调控,对结直肠癌(CRC)远处转移形成的机制的全面了解仍然是我们无法达到的。MicroRNA(miRNAs)通过在转录后水平负调控靶基因的表达而参与包括癌症在内的多种人类疾病。然而,目前关于miRNA畸变在结直肠癌肝转移中的作用的研究较少。为了确定与人类结直肠癌肝转移相关的miRNA表达模式,使用microRNA微阵列研究了具有肝转移的结直肠癌组织及其非转移对应物的miRNA表达谱,并通过定量RT-PCR进一步证实。我们发现28个miRNAs在有肝转移的结直肠癌中与无肝转移的结直肠癌相比有差异表达。其中miR-150 *、miR-125 b-2 *、miR-1179和miR-139 - 3p 4种miRNA在结直肠癌肝转移中表达上调,其余均表达下调。通过基因本体和KEGG功能分析,预测了失调控miRNAs的靶基因,发现失调控miRNAs靶向的高富集区和特异性通路参与了人结直肠癌肝转移过程。我们的研究结果表明,miRNA不仅参与结直肠癌的发生,而且还可能参与人类结直肠癌肝转移的进展。
At present, a full understanding of the mechanisms by which colorectal cancer (CRC) distant metastases form is still beyond our reach because of the intricate regulation of gene expression. MicroRNAs (miRNAs) are shown to be involved in various human diseases including cancers through negative regulation of target gene expression at the post-transcriptional level. However, there are only a few studies on the roles of miRNA aberrations in liver metastasis of human colorectal cancer. To identify miRNA expression patterns associated with liver metastasis in human colorectal cancer, the miRNA expression profiles of colorectal cancer tissues with liver metastasis and their non-metastatic counterparts were studied using microRNA microarrays and further confirmed by quantitative RT-PCR. We show that 28 miRNAs are differentially expressed in the colorectal carcinomas with liver metastasis compared to the non-metastatic counterparts. Of these, 4 miRNAs including miR150*, miR-125b-2*, miR-1179 and miR-139-3p were up-regulated in colorectal cancers with liver metastasis while the others were down-regulated. The target genes of selected deregulated miRNAs were predicted through bioinformatic techniques with two functional analyses, gene ontology and KEGG analysis, which showed that categories of high enrichment GOs and specific pathways targeted by dysregulated miRNAs were involved in liver metastasis during human colorectum carcinogenesis. Our results indicated that miRNAs are not only involved in carcinogenesis of colorectum, but may also participate in the progression such as with liver metastases in human colorectal cancers.