生物谷报道：最新研究发现，一种特殊小分子能阻碍癌症抑制基因的活性，从而使肝癌细胞生长并扩散。
这种分子属于microRNA，microRNA是最近发现的负责控制细胞产生蛋白种类和数量的小分子。目前已发现了超过250种不同的microRNA，其中数种和癌症有关。而新发现显示一种特殊分子miR-21如何使癌症发展。
研究分析了基因PTEN，它保护细胞不至于癌变。科学家发现，对这种癌症抑制基因的异常阻碍会导致肝癌等。以上结果将帮助解释肝癌发生的原因以及找到治疗这种疾病的新药。同时该RNA能作为患者预后的标志之一。
美国俄亥俄州立大学癌症中心科学家的研究结果发表在8月的Gastroenterology上。
小组发现高浓度的miR-21将阻碍PTEN基因，这激发了促使癌症增生、转移和入侵其它组织的化学路径，以上都是癌症的特征。主要负责人Tushar Patel和同事测量了存在于正常肝细胞和肝癌细胞中的197种microRNA的浓度。结果显示，肝癌组织中miR-21的浓度比正常肝细胞高出9倍。
在Patel进行的较早期研究中曾发现miR-21或许是针对PTEN的，现在这一发现确认了以上结果。更重要的是，科学家发现在正常肝细胞中增加miR-21能导致PTEN水平下降。小组同时追踪了使细胞增生、转移和入侵其它组织的化学路径。
?Patel说：“我们的研究证实miR-21在癌症发育中起到了基础作用，这或许还和其它miR-21过度表达的肿瘤有关。如果能在其它癌症研究中得到确认，那它将是一个重要进展。”（ 教育部科技发展中心）
原文链接http://www.physorg.com/news105207739.html
原始出处:
Gastroenterology
Volume 133, Issue 2, Pages 647-658 (August 2007)
MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer
Fanyin Meng⁎‡, Roger Henson⁎, Hania Wehbe–Janek⁎, Kalpana Ghoshal§, Samson T. Jacob§, Tushar Patel⁎‡</FORM>-->
Received 13 October 2006; accepted 3 May 2007. published online 22 May 2007.
Background & Aims: microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression negatively. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNA to tumor biology has not been established. Methods: We evaluated the expression of miRNA in human hepatocellular cancer (HCC) by expression profiling, and defined a target gene and biologically functional effect of an up-regulated miRNA. Results: miR-21 was noted to be highly overexpressed in HCC tumors and cell lines in expression profiling studies using a miRNA microarray. Inhibition of miR-21 in cultured HCC cells increased expression of the phosphatase and tensin homolog (PTEN) tumor suppressor, and decreased tumor cell proliferation, migration, and invasion. In contrast-enhanced miR-21 expression by transfection with precursor miR-21 increased tumor cell proliferation, migration, and invasion. Moreover, an increase in cell migration was observed in normal human hepatocytes transfected with precursor miR-21. PTEN was shown to be a direct target of miR-21, and to contribute to miR-21 effects on cell invasion. Modulation of miR-21 altered focal adhesion kinase phosphorylation and expression of matrix metalloproteases 2 and 9, both downstream mediators of PTEN involved in cell migration and invasion. Conclusions: Aberrant expression of miR-21 can contribute to HCC growth and spread by modulating PTEN expression and PTEN-dependent pathways involved in mediating phenotypic characteristics of cancer cells such as cell growth, migration, and invasion.
Abbreviations used in this paper: FAK, focal adhesion kinase, miRNA, microRNA, MMP, matrix metalloprotease, PCR, polymerase chain reaction, PTEN, phosphatase and tensin homolog, siRNA, small interfering RNA
⁎ Department of Internal Medicine, Scott and White Clinic, Texas A&M University System Health Science Center College of Medicine, Temple, Texas
‡ Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio
§ Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, Columbus, Ohio
Address requests for reprints to: Tushar Patel, MBChB, The Ohio State University Medical Center, N2 Doan Hall, 410 West 10th Avenue, Columbus, Ohio 43210.
Supported by the Scott and White Hospital Foundation, and by grants DK069370 and CA122694 from the National Institutes of Health.
PII: S0016-5085(07)01002-5
doi:10.1053/j.gastro.2007.05.022
© 2007 AGA Institute. Published by Elsevier Inc. All rights reserved.
