Department of Gastroenterology of Taizhou People's Hospital, Soochow University, Jiangsu Province, Shanghai, PR China.
Oncol Rep. 2011 Mar;25(3):739-47. doi: 10.3892/or.2010.1112. Epub 2010 Dec 20.
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 miR-150*, 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.
目前,由于基因表达的复杂调控,我们仍然无法完全了解结直肠癌(CRC)远处转移形成的机制。研究表明,微小 RNA(miRNA)通过在转录后水平负调控靶基因的表达,参与包括癌症在内的各种人类疾病。然而,关于 miRNA 异常在人类结直肠癌肝转移中的作用的研究还很少。为了鉴定与人类结直肠癌肝转移相关的 miRNA 表达模式,我们使用 miRNA 微阵列研究了具有肝转移和无转移结直肠癌组织的 miRNA 表达谱,并通过定量 RT-PCR 进一步证实。我们表明,与无转移的结直肠癌相比,有 28 个 miRNA 在具有肝转移的结直肠癌中表达差异。其中,miR-150*、miR-125b-2*、miR-1179 和 miR-139-3p 在具有肝转移的结直肠癌中上调,而其他 miRNA 下调。通过生物信息学技术,对选定的失调 miRNA 的靶基因进行预测,通过两个功能分析,GO 和 KEGG 分析,结果表明,失调 miRNA 靶向的高富集 GO 类别和特定途径参与了人类结直肠癌变过程中的肝转移。我们的结果表明,miRNA 不仅参与了结直肠癌的发生,而且可能参与了结直肠癌的进展,如肝转移。