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微小RNA-21介导的肿瘤生长。

miR-21-mediated tumor growth.

作者信息

Si M-L, Zhu S, Wu H, Lu Z, Wu F, Mo Y-Y

机构信息

Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.

出版信息

Oncogene. 2007 Apr 26;26(19):2799-803. doi: 10.1038/sj.onc.1210083. Epub 2006 Oct 30.

Abstract

MicroRNAs (miRNAs) are approximately 22 nucleotide non-coding RNA molecules that regulate 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.

摘要

微小RNA(miRNA)是约22个核苷酸的非编码RNA分子,可在转录后水平调节基因表达。尽管miRNA在各种人类癌症中的异常表达提示其在肿瘤发生中起作用,但敲低特定miRNA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阵列方法分析了配对的正常乳腺组织和乳腺肿瘤组织中的miRNA表达。与先前的研究结果一致,我们发现在分析的157个人类miRNA中,与配对的正常乳腺组织相比,miR-21在乳腺肿瘤中高度过表达。为了更好地评估miR-21在肿瘤发生中的作用,我们用抗miR-21寡核苷酸转染乳腺癌MCF-7细胞,发现抗miR-21在体外抑制细胞生长,并在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,这可能部分归因于抗miR-21处理的肿瘤细胞中抗凋亡蛋白Bcl-2的下调。总之,这些结果表明miR-21作为一种癌基因发挥作用,并通过调节诸如bcl-2等基因来调控肿瘤发生,因此,它可能成为一个新的治疗靶点。

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