Identification of miR-145 targets through an integrated omics analysis.
Identification of miR-145 targets through an integrated omics analysis.
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DOI：
10.1039/c4mb00585f
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发表时间：
2015-01
影响因子：
--
通讯作者：
Pandey A
中科院分区：
文献类型：
--
作者：
Huang TC;Renuse S;Pinto S;Kumar P;Yang Y;Chaerkady R;Godsey B;Mendell JT;Halushka MK;Civin CI;Marchionni L;Pandey A
microRNAs（miRNAs）是一类调控基因表达和蛋白质合成的非编码小分子RNA。为了表征miRNA的功能并评估其潜在的应用，我们进行了一个综合的多组学分析，以研究miR-145，一种已被证明可以抑制肿瘤生长的miRNA。我们对胰腺癌细胞系进行了基因表达谱、miRNA谱和定量蛋白质组学分析。在我们的转录组学分析中，发现miR-145的过表达抑制了与癌症发展有关的基因的表达，如ITGA 11和MAGEA 4，以及先前描述的靶点，如FSCN 1，YES 1和PODXL。基于miRNA谱，miR-145的过表达也上调了其他miRNA，包括miR-124、miR-133 b和miR-125 a-3 p，所有这些都涉及肿瘤的抑制，并且通常与其他癌症中的miR-145共调节。使用SILAC系统，我们鉴定了miR-145诱导的几种癌蛋白/癌症生物标志物的下调，包括SET、RPA 1、MCM 2、ABCC 1、SPTBN 1和SPTLC 1。对下调的候选靶标的子集进行的荧光素酶测定验证证实它们是miR-145的新的直接靶标。总体而言，这种多组学方法提供了对miR-145介导的肿瘤抑制的见解，并可用作研究单个miRNA靶点的一般策略。
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and protein synthesis. To characterize functions of miRNAs and to assess their potential applications, we carried out an integrated multi-omics analysis to study miR-145, a miRNA that has been shown to suppress tumor growth. We employed gene expression profiling, miRNA profiling and quantitative proteomic analysis of a pancreatic cancer cell line. In our transcriptomic analysis, overexpression of miR-145 was found to suppress the expression of genes that are implicated in development of cancer such as ITGA11 and MAGEA4 in addition to previously described targets such as FSCN1, YES1 and PODXL. Based on miRNA profiling, overexpression of miR-145 also upregulated other miRNAs including miR-124, miR-133b and miR-125a-3p, all of which are implicated in suppression of tumors and are generally co-regulated with miR-145 in other cancers. Using the SILAC system, we identified miR-145-induced downregulation of several oncoproteins/cancer biomarkers including SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1. Luciferase assay validation carried out on a subset of downregulated candidate targets confirmed them to be novel direct targets of miR-145. Overall, this multi-omics approach provided insights into miR-145-mediated tumor suppression and could be used as a general strategy to study the targets of individual miRNAs.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
3.4
作者：
Di Leva G;Briskin D;Croce CM
通讯作者：
Croce CM
影响因子：
3.7
作者：
Gregersen LH;Jacobsen AB;Frankel LB;Wen J;Krogh A;Lund AH
通讯作者：
Lund AH
影响因子：
3
作者：
Campanini, Marina Lanciotti;Colli, Leandro Machado;de Castro, Margaret
通讯作者：
de Castro, Margaret
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y