RNAi热门文章：miR21靶向治疗癌症

　　

生物通报道，新一期的The Scientist公布了近期热门的癌症靶向治疗文章，该文章由美国南伊利诺伊州大学医学院的肿瘤生物学家Yin-Yuan Mo发表在2007年的Journal of Biological Chemistry上，目前已被76篇文章引用。文章标题为：MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM 1)。

 

领导这一研究的是南伊利诺伊州大学医学院的肿瘤细胞生物学家Yin-Yuan Mo，Mo的研究小组阻断了小鼠的恶性肿瘤细胞中的miR-21后观察肿瘤细胞中的蛋白表达水平情况。miR21是一种与癌症相关的小RNA，主要参与基因表达调控作用。研究小组发现，miR-21主要通过沉默肿瘤抑制基因（TPM1）促进肿瘤生长。

 

该文章的重要意义

加州大学的一名神经科学家Kenneth Kosik称，这篇文章的重大贡献在于让人们了解microRNA驱动癌症的机制，并首先鉴定出癌症靶位miR21。Kenneth Kosik也是研究miR-21的专家。文章作者Mo称，该研究中的高通量蛋白组检测方法为鉴定microRNA靶位提供可靠的方式，传统的方法检测microRNA的序列常常导致假阳性结果，新的方法可有效规避这一缺陷。

 

目前miR21已经成为癌症治疗的热门研究靶位。

（生物通 小茜）

生物通推荐原文检索：MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM 1)

【Abstract】

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that mir-21 is overexpressed in tumor tissues compared with the matched normal tissues. Moreover, suppression of mir-21 by antisense oligonucleotides inhibits tumor cell growth both in vitro and in vivo. However, it remains largely unclear as to how mir-21 affects tumor growth, because our understanding of mir-21 targets is limited. In this study, we performed two-dimensional differentiation in-gel electrophoresis of tumors treated with anti-mir-21 and identified the tumor suppressor tropomyosin 1 (TPM1) as a potential mir-21 target. In agreement with this, there is a putative mir-21 binding site at the 3'-untranslated region (3'-UTR) of TPM1 variants V1 and V5. Thus, we cloned the 3'-UTR of TPM1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. Moreover, deletion of the mir-21 binding site abolished the effect of mir-21 on the luciferase activity, suggesting that this mir-21 binding site is critical. Western blot with the cloned TPM1-V1 plus the 3'-UTR indicated that TPM1 protein level was also regulated by mir-21, whereas real-time quantitative reverse transcription-PCR revealed no difference at the mRNA level, suggesting translational regulation. Finally, overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth. Thus, down-regulation of TPM1 by mir-21 may explain, at least in part, why suppression of mir-21 can inhibit tumor growth, further supporting the notion that mir-21 functions as an oncogene.