Lessons from miR-143/145: the importance of cell-type localization of miRNAs.
Lessons from miR-143/145: the importance of cell-type localization of miRNAs.
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DOI：
10.1093/nar/gku461
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Halushka MK
中科院分区：
文献类型：
--
作者：
Kent OA;McCall MN;Cornish TC;Halushka MK
MiR-143和miR-145是共表达的microRNAs，被广泛研究为潜在的肿瘤抑制因子。这些miRNAs在结肠中高度表达，并一直被报道在结直肠癌和其他癌症中表达下调。通过调节多个靶点，它们在癌细胞生长和肿瘤形成方面产生了强大的作用。重要的是，最近的一项发现表明miR-143和miR-145在结肠上皮细胞中不表达；相反，这两个miRNAs在成纤维细胞和平滑肌细胞等间充质细胞中高表达。MiR-143和miR-145以及其他miRNAs的表达模式最初是根据组织水平的数据确定的，没有考虑到多个不同的细胞类型，每种细胞类型都有自己独特的miRNA表达模式，组成每个组织。在这里，我们讨论了早期关于结直肠癌中miR-143和miR-145表达异常的报道，以及缺乏对正常组织细胞成分的考虑是如何导致错误地认为这些miRNAs在癌症中下调的。我们根据miR-143/145研究的细胞类型限制性表达模式和这些miRNAs被认为是肿瘤抑制因子的潜力来评估机制数据。此外，我们检查了其他例子的miRNAs被研究在不适当的细胞类型调制途径以非生物的方式。我们的综述强调了确定每个miRNA的细胞表达模式的重要性，以便在适当的细胞类型中进行下游研究。
miR-143 and miR-145 are co-expressed microRNAs (miRNAs) that have been extensively studied as potential tumor suppressors. These miRNAs are highly expressed in the colon and are consistently reported as being downregulated in colorectal and other cancers. Through regulation of multiple targets, they elicit potent effects on cancer cell growth and tumorigenesis. Importantly, a recent discovery demonstrates that miR-143 and miR-145 are not expressed in colonic epithelial cells; rather, these two miRNAs are highly expressed in mesenchymal cells such as fibroblasts and smooth muscle cells. The expression patterns of miR-143 and miR-145 and other miRNAs were initially determined from tissue level data without consideration that multiple different cell types, each with their own unique miRNA expression patterns, make up each tissue. Herein, we discuss the early reports on the identification of dysregulated miR-143 and miR-145 expression in colorectal cancer and how lack of consideration of cellular composition of normal tissue led to the misconception that these miRNAs are downregulated in cancer. We evaluate mechanistic data from miR-143/145 studies in context of their cell type-restricted expression pattern and the potential of these miRNAs to be considered tumor suppressors. Further, we examine other examples of miRNAs being investigated in inappropriate cell types modulating pathways in a non-biological fashion. Our review highlights the importance of determining the cellular expression pattern of each miRNA, so that downstream studies are conducted in the appropriate cell type.
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影响因子：
3.7
作者：
Feng X;Wang H;Ye S;Guan J;Tan W;Cheng S;Wei G;Wu W;Wu F;Zhou Y
通讯作者：
Zhou Y
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
6.4
作者：
Gits, Caroline M. M.;van Kuijk, Patricia F.;Wiemer, Erik A. C.
通讯作者：
Wiemer, Erik A. C.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.