因感染或慢性肠炎等疾病而引发的慢性炎症与近四分之一的癌症相关。然而，它们之间到底存在着什么样的关联呢？最近，PNAS杂志上的一篇论文讲述了炎症如何导致癌症。
这篇论文的作者是俄亥俄州立大学医学中心和综合癌症中心的研究人员，他们发现炎症刺激了一种microRNA分子（miR-155）水平的升高。这导致参与DNA修复的蛋白水平下降，使基因自发突变率更高，从而导致癌症。
文章的第一作者Esmerina Tili博士谈到：“人们怀疑炎症在癌症中扮演了重要角色，而我们的研究提出了一种分子机制。研究表明炎症刺激上调了miR-155，而miR-155的过表达又提高了自发突变率，这可能导致肿瘤生成。”
MicroRNA（miRNA）虽然只有短短22个碱基，但却在体内发挥着重要的基因表达调控作用。它们通过抑制特定蛋白的表达来执行调控功能，一个miRNA可能调控了若干个蛋白，而一个蛋白又受到多个miRNA的调控。
miR-155这种分子能影响血细胞成熟，免疫反应和自体免疫疾病，而高水平的分子更是与白血病、乳腺癌、肺癌等疾病直接关联。
在这项研究中，Till和她的同事研究了促炎症物质（如肿瘤坏死因子或脂多糖）对miR-155表达以及对几种乳腺癌细胞系中自发突变频率的影响。
当乳腺癌细胞暴露在两种炎症因子下，miR-155水平异常升高，突变率也提高2-3倍。为了研究这种现象出现的原因，她们将目光投向WEE1基因，这种基因停止了细胞分裂的过程，让受损DNA得以修复。
研究人员知道miR-155会靶定WEE1，且高水平的miR-155导致了低水平的WEE1。她们推断，低水平的WEE1让存在DNA损伤的细胞继续分裂，从而产生更多突变。
俄亥俄州立大学的PI Carlo M. Croce教授表示：“普遍认为，癌症是由机体细胞的突变累积而引发的。我们的研究表明miR-155提高了突变率，可能在炎症引发的癌症中扮演了关键角色。”
这项研究成果表明，miR-155可能成为一个新的治疗靶点，那些能降低miR-155水平的药物有望改善炎症相关癌症的治疗。（生物谷Bioon.com）
生物谷推荐原文出处：
Proceedings of the National Academy of Sciences DOI：10.1073/pnas.1101795108
Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer
Tili, Esmerina; Michaille, Jean-Jacques; Wernicke, Dorothee; Alder, Hansjuerg; Costinean, Stefan; Volinia, Stefano; Croce, Carlo M.
Infection-driven inflammation has been implicated in the pathogenesis of ~15–20% of human tumors. Expression of microRNA-155(miR-155) is elevated during innate immune response and autoimmune disorders as well as in various malignancies. However, the molecularmechanisms providing miR-155 with its oncogenic properties remain unclear. We examined the effects of miR-155 overexpression and proinflammatory environment on the frequency of spontaneous hypoxanthine phosphoribosyltransferase (HPRT) mutations that can be detected based on the resistance to 6-thioguanine. Both miR-155 overexpression and inflammatory environment increased the frequency of HPRT mutations and down-regulated WEE1 (WEE1 homolog-S. pombe), a kinase that blocks cell-cycle progression. The increased frequencyof HPRT mutation was only modestly attributable to defects in mismatch repair machinery. This result suggests that miR-155 enhances the mutation rate by simultaneously targeting different genes that suppress mutations and decreasing the efficiencyof DNA safeguard mechanisms by targeting of cell-cycle regulators such as WEE1. By simultaneously targeting tumor suppressorgenes and inducing a mutator phenotype, miR-155 may allow the selection of gene alterations required for tumor development and progression. Hence, we anticipate that thedevelopment of drugs reducing endogenous miR-155 levels might be key in the treatment of inflammation-related cancers.
