生物谷報(bào)道：最新研究發(fā)現(xiàn)，一種特殊小分子能阻礙癌癥抑制基因的活性,，從而使肝癌細(xì)胞生長并擴(kuò)散,。
這種分子屬于microRNA，microRNA是最近發(fā)現(xiàn)的負(fù)責(zé)控制細(xì)胞產(chǎn)生蛋白種類和數(shù)量的小分子,。目前已發(fā)現(xiàn)了超過250種不同的microRNA,，其中數(shù)種和癌癥有關(guān)。而新發(fā)現(xiàn)顯示一種特殊分子miR-21如何使癌癥發(fā)展,。
研究分析了基因PTEN,，它保護(hù)細(xì)胞不至于癌變,?？茖W(xué)家發(fā)現(xiàn)，對(duì)這種癌癥抑制基因的異常阻礙會(huì)導(dǎo)致肝癌等,。以上結(jié)果將幫助解釋肝癌發(fā)生的原因以及找到治療這種疾病的新藥,。同時(shí)該RNA能作為患者預(yù)后的標(biāo)志之一。
美國俄亥俄州立大學(xué)癌癥中心科學(xué)家的研究結(jié)果發(fā)表在8月的Gastroenterology上,。
小組發(fā)現(xiàn)高濃度的miR-21將阻礙PTEN基因,，這激發(fā)了促使癌癥增生、轉(zhuǎn)移和入侵其它組織的化學(xué)路徑,，以上都是癌癥的特征,。主要負(fù)責(zé)人Tushar Patel和同事測(cè)量了存在于正常肝細(xì)胞和肝癌細(xì)胞中的197種microRNA的濃度。結(jié)果顯示,，肝癌組織中miR-21的濃度比正常肝細(xì)胞高出9倍,。
在Patel進(jìn)行的較早期研究中曾發(fā)現(xiàn)miR-21或許是針對(duì)PTEN的，現(xiàn)在這一發(fā)現(xiàn)確認(rèn)了以上結(jié)果,。更重要的是,，科學(xué)家發(fā)現(xiàn)在正常肝細(xì)胞中增加miR-21能導(dǎo)致PTEN水平下降,。小組同時(shí)追蹤了使細(xì)胞增生、轉(zhuǎn)移和入侵其它組織的化學(xué)路徑,。
?Patel說：“我們的研究證實(shí)miR-21在癌癥發(fā)育中起到了基礎(chǔ)作用,，這或許還和其它miR-21過度表達(dá)的腫瘤有關(guān)。如果能在其它癌癥研究中得到確認(rèn),，那它將是一個(gè)重要進(jìn)展,。”（ 教育部科技發(fā)展中心）
原文鏈接http://www.physorg.com/news105207739.html
原始出處:
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.
