MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells.
MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells.
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DOI：
10.1186/s12929-014-0095-x
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发表时间：
2014-10-05
影响因子：
11
通讯作者：
Huang CJ
中科院分区：
文献类型：
--
作者：
Choo KB;Soon YL;Nguyen PN;Hiew MS;Huang CJ
两种成熟的miRNA种类可以从pre-miRNA前体的5'和3'臂产生。在大多数情况下，只剩下一个物种，而互补物种则退化。然而，越来越多地报道了miRNA-5 p和-3p种类的共存。在这项工作中，我们的目的是系统地研究在全基因组分析中，miRNA-5 p/3 p在结肠癌细胞中的共表达，并检查失调的miRNA和5 p/3 p种类的交叉靶向。相对于两个正常结肠组织检查四个结肠癌细胞系。在分析的1，190种miRNAs中，发现92种和36种在癌细胞中分别上调或下调。进一步鉴定了19个共表达的miRNA-5 p/3 p对，表明在结肠癌细胞中频繁的5 p/3 p共积累。其中，14对共上调，3对共下调，表明协调的5 p/3 p失调。9对表达异常的miRNA分别属于let-7、mir-8/200和mir-17 3个miRNA基因家族，在肿瘤转移过程中表现出频繁的交叉靶向作用。关注let-7 d-5 p/3 p对，显示分别靶向的IGF 1 R和KRAS与相应miRNA的表达呈反向关系，这在使用let-7 d模拟物或抑制剂的瞬时转染测定中得到证实。之前报道了let-7 d对KRAS的靶向作用;本研究中，在荧光素酶测定中证实了let-7 d-5 p对IGF 1 R的靶向作用。let-7 d-5 p/3 p和其他多种靶向IGF 1 R、KRAS和其他转移相关因子的miRNAs的发现表明，5 p/3 p miRNAs有助于交叉靶向多种癌症相关因子，并可能在任何一种关键因子失活时避免功能性废除。miRNA-5 p/3 p种类在结肠癌细胞中经常共表达并协调调节。在癌细胞中，miRNA的多重交叉靶向，包括共存的5 p/3 p种类，经常发生在重要肿瘤发生过程的miRNA调节的明显安全方案中。进一步系统分析临床组织中共存的miRNA-5 p/3 p对对于阐明5 p/3 p对癌症发病机制的贡献是重要的。本文的在线版本（doi：10.1186/s12929-014-0095-x）包含补充材料，可供授权用户使用。
Two mature miRNA species may be generated from the 5’ and 3’ arms of a pre-miRNA precursor. In most cases, only one species remains while the complementary species is degraded. However, co-existence of miRNA-5p and -3p species is increasingly being reported. In this work, we aimed to systematically investigate co-expression of miRNA-5p/3p in colon cancer cells in a genome-wide analysis, and to examine cross-targeting of the dysregulated miRNAs and 5p/3p species. Four colon cancer cell lines were examined relative to two normal colon tissues. Of the 1,190 miRNAs analyzed, 92 and 36 were found to be up- or down-regulated, respectively, in cancer cells. Nineteen co-expressed miRNA-5p/3p pairs were further identified suggesting frequent 5p/3p co-accumulation in colon cancer cells. Of these, 14 pairs were co-up-regulated and 3 pairs were co-down-regulated indicating concerted 5p/3p dysregulation. Nine dysregulated miRNA pairs fell into three miRNA gene families, namely let-7, mir-8/200 and mir-17, which showed frequent cross-targeting in the metastasis process. Focusing on the let-7d-5p/3p pair, the respectively targeted IGF1R and KRAS were shown to be in a reverse relationship with expression of the respective miRNA, which was confirmed in transient transfection assays using let-7d mimic or inhibitor. Targeting of KRAS by let-7d was previous reported; targeting of IGF1R by let-7d-5p was confirmed in luciferase assays in this study. The findings of let-7d-5p/3p and multiple other miRNAs targeting IGF1R, KRAS and other metastasis-related factors suggest that 5p/3p miRNAs contribute to cross-targeting of multiple cancer-associated factors and processes possibly to evade functional abolishment when any one of the crucial factors are inactivated. miRNA-5p/3p species are frequently co-expressed and are coordinately regulated in colon cancer cells. In cancer cells, multiple cross-targeting by the miRNAs, including the co-existing 5p/3p species, frequently occurs in an apparent safe-proof scheme of miRNA regulation of important tumorigenesis processes. Further systematic analysis of co-existing miRNA-5p/3p pairs in clinical tissues is important in elucidating 5p/3p contributions to cancer pathogenesis. The online version of this article (doi:10.1186/s12929-014-0095-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Biasiolo M;Sales G;Lionetti M;Agnelli L;Todoerti K;Bisognin A;Coppe A;Romualdi C;Neri A;Bortoluzzi S
通讯作者：
Bortoluzzi S
影响因子：
3.7
作者：
Drusco A;Nuovo GJ;Zanesi N;Di Leva G;Pichiorri F;Volinia S;Fernandez C;Antenucci A;Costinean S;Bottoni A;Rosito IA;Liu CG;Burch A;Acunzo M;Pekarsky Y;Alder H;Ciardi A;Croce CM
通讯作者：
Croce CM
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
DOI：
10.1073/pnas.0812591106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Jazdzewski, Krystian;Liyanarachchi, Sandya;De la Chapelle, Albert
通讯作者：
De la Chapelle, Albert
影响因子：
24.5
作者：
Freier, S;Weiss, O;Raz, I
通讯作者：
Raz, I