miR-21-mediated tumor growth
miR-21-mediated tumor growth
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DOI：
10.1038/sj.onc.1210083
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发表时间：
2007-04-26
期刊：
影响因子：
8
通讯作者：
Mo, Y.-Y.
中科院分区：
文献类型：
--
作者：
Si, M.-L.;Zhu, S.;Mo, Y.-Y.
MicroRNAs （miRNAs）是B22核苷酸非编码RNA分子，在转录后调节基因表达。尽管在各种人类癌症中miRNA的异常表达表明miRNA在肿瘤发生中发挥作用，但对于特定miRNA的敲低是否会影响肿瘤生长仍不清楚。在本研究中，我们通过TaqMan实时聚合酶链反应miRNA阵列方法分析了匹配的正常乳腺组织和乳腺肿瘤组织中miRNA的表达。与先前的发现一致，我们发现在分析的157种人类mirna中，miR-21在乳腺肿瘤中与匹配的正常乳腺组织相比高度过表达。为了更好地评估miR-21在肿瘤发生中的作用，我们用anti-miR-21寡核苷酸转染乳腺癌MCF-7细胞，发现anti-miR-21在体外抑制细胞生长和异种移植小鼠模型中抑制肿瘤生长。此外，这种抗mir -21介导的细胞生长抑制与细胞凋亡增加和细胞增殖减少有关，这可能部分是由于抗mir -21处理的肿瘤细胞中抗凋亡Bcl-2的下调。总之，这些结果表明，miR-21作为一种致癌基因，通过调控bcl-2等基因来调节肿瘤的发生，因此，它可能作为一种新的治疗靶点。
MicroRNAs (miRNAs) are B22 nucleotide non-coding RNA molecules that dregulate gene expression post-transcriptionally. Although aberrant expression of miRNAs in various human cancers suggests a role for miRNAs in tumorigenesis, it remains largely unclear as to whether knockdown of a specific miRNA affects tumor growth. In this study, we profiled miRNA expression in matched normal breast tissue and breast tumor tissues by TaqMan real-time polymerase chain reaction miRNA array methods. Consistent with previous findings, we found that miR-21 was highly overexpressed in breast tumors compared to the matched normal breast tissues among 157 human miRNAs analysed. To better evaluate the role of miR-21 in tumorigenesis, we transfected breast cancer MCF-7 cells with anti-miR-21 oligonucleotides and found that anti-miR-21 suppressed both cell growth in vitro and tumor growth in the xenograft mouse model. Furthermore, this anti-miR-21-mediated cell growth inhibition was associated with increased apoptosis and decreased cell proliferation, which could be in part owing to downregulation of the antiapoptotic Bcl-2 in anti-miR-21-treated tumor cells. Together, these results suggest that miR-21 functions as an oncogene and modulates tumorigenesis through regulation of genes such as bcl-2 and thus, it may serve as a novel therapeutic target.