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微小RNA 143和145可能是人类癌症中常见的致癌微小RNA。

MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers.

作者信息

Akao Yukihiro, Nakagawa Yoshihito, Naoe Tomoki

机构信息

Gifu International Institute of Biotechnology, Gifu 504-0838, Japan.

出版信息

Oncol Rep. 2006 Oct;16(4):845-50.

PMID:16969504
Abstract

MicroRNAs (miRNAs) are endogenously expressed RNAs 18-24 nucleotides in length that regulate gene expression through translational repression by binding to a target mRNA. It is thought that the expression level of miRNAs, which act like antioncogenes, is frequently reduced in cancers because of chromosome deletion and epigenetic changes. Since the processing of miRNAs has been characterized to be enzymatic in nature, the expression levels of miRNAs are closely associated with the activity and levels of such enzymes. Here, we found that miRNA 143 and 145 expression levels were extremely reduced in colon cancer cells and commonly in the other kinds of cancer cells tested. The transfection of each precursor miRNA into the cells demonstrated a significant growth inhibition in human colon cancer DLD-1 and SW480 cells, and ERK5 was determined to be the target gene of miRNA 143. Since the presence of genomic loci of the miRNAs was confirmed by PCR in the cell lines and the precursor miRNAs exhibited a growth inhibitory effect in DLD-1 and SW480 cells, the early processes such as transcription and enzymatic modification from primary miRNAs to precursor miRNAs seemed to be commonly disturbed. These findings indicate that the miRNAs 143 and 145 could become good tumor markers and provide an important clue in the study of the mechanism of oncogenesis involving miRNAs.

摘要

微小RNA(miRNA)是长度为18 - 24个核苷酸的内源性表达RNA,其通过与靶mRNA结合进行翻译抑制来调节基因表达。人们认为,起着抑癌基因作用的miRNA的表达水平在癌症中常常因染色体缺失和表观遗传变化而降低。由于miRNA的加工本质上已被表征为酶促过程,因此miRNA的表达水平与这些酶的活性和水平密切相关。在这里,我们发现miRNA 143和145的表达水平在结肠癌细胞以及所测试的其他类型癌细胞中均极度降低。将每种前体miRNA转染到细胞中显示出对人结肠癌DLD - 1和SW480细胞有显著的生长抑制作用,并且ERK5被确定为miRNA 143的靶基因。由于通过PCR在细胞系中证实了miRNA基因组位点的存在,并且前体miRNA在DLD - 1和SW480细胞中表现出生长抑制作用,从初级miRNA到前体miRNA的转录和酶促修饰等早期过程似乎普遍受到干扰。这些发现表明,miRNA 143和145可能成为良好的肿瘤标志物,并为涉及miRNA的肿瘤发生机制研究提供重要线索。

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