Nature：牛津质疑麻省理工miRNA癌转移理论

　　

生物通报道，microRNA是一段非常短的非编码单链RNA，它们参与基因调控表达，对多种生物学过程起调控作用，近年的研究发现microRNA与癌症的发生、转移都具有密切的调节作用，有些microRNA是癌症的克星，而有些microRNA却助纣为虐帮助癌细胞扩散。关于这些或促进或抑制的microRNA，牛津大学的看法与麻省理工大学的看法有出入。

 

2007年麻省理工提出microRNA-10b促进癌细胞转移观点

在2007年9月26日的Nature上来自美国麻省理工大学白头研究所生物医学和生物学研究中心的科学家发表文章称，microRNA-10b是促进乳腺癌扩散的罪魁祸首之一。研究者认为转录失常会导致microRNA-10b过度表达，并诱导未发生转移的癌细胞开始进入转移程序。microRNA首先启动mRNA编码homeobox D10，结果促进癌症转移因子RHOC前体表达量增加。很明显的，microRNA-10b转录水平增高会导致早期乳腺癌患者预后不良，促进癌细胞扩散。

 

2008年牛津大学科学家质疑microRNA-10b促进癌症转移理论

2008年10月23日新鲜出炉的Nature上，来自英国牛津大学Weatherall 分子医学研究所英国癌症分子肿瘤实验室联手Wellcome Trust 人类遗传学研究中心遗传研究组开展发表最新文章，质疑麻省理工大学2007年提出的microRNA-10b促进乳腺癌细胞扩散的理论。

该研究小组的科学家通过对92名乳腺癌转移患者和127名乳腺癌无转移病况患者进行遗传学检测，结果他们发现乳腺癌细胞的转移与microRNA-10b表达水平没有直接的联系。

但是研究小组承认，在肿瘤细胞生长的前期，microRNA-10b可能对少量的细胞具有生物学作用，但是并不能就此认为microRNA-10b就是对整个癌转移病程具有推动作用的调节因子。

 

麻省理工microRNA文章检索：直接点击进入链接

Tumour invasion and metastasis initiated by microRNA-10b in breast cancer

 

【Abstract】

MicroRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumour suppressors, the role of microRNAs in mediating cancer metastasis remains unexplored. Here we show, using a combination of mouse and human cells, that microRNA-10b (miR-10b) is highly expressed in metastatic breast cancer cells and positively regulates cell migration and invasion. Overexpression of miR-10b in otherwise non-metastatic breast tumours initiates robust invasion and metastasis. Expression of miR-10b is induced by the transcription factor Twist, which binds directly to the putative promoter of mir-10b (MIRN10B). The miR-10b induced by Twist proceeds to inhibit translation of the messenger RNA encoding homeobox D10, resulting in increased expression of a well-characterized pro-metastatic gene, RHOC. Significantly, the level of miR-10b expression in primary breast carcinomas correlates with clinical progression. These findings suggest the workings of an undescribed regulatory pathway, in which a pleiotropic transcription factor induces expression of a specific microRNA, which suppresses its direct target and in turn activates another pro-metastatic gene, leading to tumour cell invasion and metastasis.

 

 牛津microRNA文章检索：直接点击进入连接

MicroRNA-10b and breast cancer metastasis

 

【Abstract】

MicroRNAs regulate messenger RNA expression but are frequently dysregulated in tumours. Ma et al. 1 report that overexpression of microRNA-10b (miR-10b) initiates invasion and metastasis in models of breast cancer and that its expression in primary breast carcinomas correlates with clinical progression. We tested this in patients with primary breast cancer, of whom 92 had nodal metastases at diagnosis and 127 were node-negative. We found no significant association between miR-10b levels and metastasis or prognosis. Although we concede that miR-10b may have a biological effect in a few cells at the growing edge of a tumour, we believe that it is unlikely to correlate in whole tumour samples with clinical progression.

生物通 张欢