New target genes of MITF-induced microRNA-211 contribute to melanoma cell invasion.
New target genes of MITF-induced microRNA-211 contribute to melanoma cell invasion.
复制标题
DOI：
10.1371/journal.pone.0073473
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kreis S
中科院分区：
文献类型：
--
作者：
Margue C;Philippidou D;Reinsbach SE;Schmitt M;Behrmann I;Kreis S
非编码microRNA（miRNA）具有组织和疾病特异性表达模式。它们下调靶mRNA，这可能影响大多数基本的细胞过程。目前正在利用miRNA的差异表达模式来鉴定用于早期疾病诊断的生物标志物，预测黑色素瘤和其他癌症的进展，以及作为有前途的药物靶标，因为它们可以在给定的细胞环境中容易地被抑制或取代。在临床上成功地操纵miRNA之前，必须确定其精确的表达水平、内源性功能以及因此确定其靶基因。MiR-211是一种黑素细胞谱系特异性的非编码小RNA，位于小眼症相关转录因子（MITF）的靶基因TRPM 1的内含子中。通过转录上调TRPM 1，MITF对黑素细胞分化和存活以及黑色素瘤进展至关重要，间接驱动miR-211的表达。这种miRNA的表达通常在黑素瘤样品中减少。在这里，我们通过识别和研究新的靶基因来研究miR-211的功能作用。我们发现，与正常黑素细胞和痣相比，MITF相关的miR-211表达水平在一组11种黑色素瘤细胞系以及原发性和转移性黑色素瘤中主要但不总是降低。miR-211本身对细胞侵袭和迁移的影响很小，而一些新的miR-211靶基因，如AP 1 S2、SOX 11、IGFBP 5和SERINC 3的干扰显著增加了侵袭。这些结果和miR-211的可变表达水平引起了对miR-211作为黑色素瘤肿瘤抑制miRNA和/或作为黑色素瘤生物标志物的价值的严重怀疑。
The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF). By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.
登录
查看更多内容
影响因子：
7.4
作者：
Jukic DM;Rao UN;Kelly L;Skaf JS;Drogowski LM;Kirkwood JM;Panelli MC
通讯作者：
Panelli MC
影响因子：
3.7
作者：
Pollari S;Leivonen SK;Perälä M;Fey V;Käkönen SM;Kallioniemi O
通讯作者：
Kallioniemi O
影响因子：
3.7
作者：
Cai C;Ashktorab H;Pang X;Zhao Y;Sha W;Liu Y;Gu X
通讯作者：
Gu X
影响因子：
16
作者：
Levy C;Khaled M;Iliopoulos D;Janas MM;Schubert S;Pinner S;Chen PH;Li S;Fletcher AL;Yokoyama S;Scott KL;Garraway LA;Song JS;Granter SR;Turley SJ;Fisher DE;Novina CD
通讯作者：
Novina CD
影响因子：
6.5
作者：
Mueller, Daniel W.;Rehli, Michael;Bosserhoff, Anja K.
通讯作者：
Bosserhoff, Anja K.