Identification of non-coding RNAs embracing microRNA-143/145 cluster.

Identification of non-coding RNAs embracing microRNA-143/145 cluster.
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DOI:
10.1186/1476-4598-9-136
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发表时间:
2010-06-02
期刊:
影响因子:
37.3
通讯作者:
Akao Y
Akao Y
中科院分区:
医学1区
文献类型:
--
作者:
Iio A;Nakagawa Y;Hirata I;Naoe T;Akao Y

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在各种癌症中,报道了microRNA(miRNA)表达模式的改变,并且可能影响细胞周期和细胞存活。最近的研究表明,作为肿瘤抑制因子的miRNA的表达水平在癌症中经常降低,这是由于染色体缺失、表观遗传变化、异常转录和miRNA加工的干扰。miR-143和-145位于染色体5 q33处,彼此相距约1.3 kb,在几种组织中高度表达,但在大多数癌症中下调。然而,这种下调的机制尚未被详细研究。在这里,我们发现这两种miRNAs在相同的控制程序下在人体组织中表达良好,但在大多数测试的癌细胞系中同样下调。然后我们鉴定了编码这两种miRNAs的宿主基因。该基因的转录物约为11,7.5和5.5 kb长;这些转录物的表达与其常驻miRNA的表达协调,并且在测试的癌细胞系以及结直肠癌组织样品中下调。这些数据表明宿主基因可以作为初级miRNA转录物起作用,并表明宿主基因表达的下调导致其编码的microRNA-143和-145在人癌细胞系和癌组织中的低表达。
In a variety of cancers, altered patterns of microRNA (miRNA) expression are reported and may affect the cell cycle and cell survival. Recent studies suggest that the expression level of miRNAs that act as tumor suppressors is frequently reduced in cancers because of chromosome deletions, epigenetical changes, aberrant transcription and disturbances in miRNA processing. miR-143 and -145, which are located approximately 1.3 kb from each other at chromosome 5q33, are highly expressed in several tissues, but down-regulated in most cancers. However, the mechanism of this down-regulation has not been investigated in detail. Here, we show that both miRNAs were expressed well under the same control program in human tissues, but were down-regulated equally in the most of the cancer cell lines tested. Then we identified the host gene encoding both miRNAs. The transcripts of this gene were approximately 11, 7.5, and 5.5 kb long; and the expression of these transcripts was coordinated with that of its resident miRNAs and down-regulated in the cancer cell lines tested as well as in colorectal cancer tissue samples. These data demonstrate that the host gene can function as a primary miRNA transcript and suggest that the down-regulation of host gene expression caused the low-expression of its encoded microRNAs-143 and -145 in human cancer cell lines and in cancer tissues.
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