特殊microRNA或可帮助开发治疗胰腺癌的新型手段

  来自印第安纳大学(Indiana University)的研究人员近日通过研究发现，一种特殊的microRNA或可有效抵御胰腺癌的发展，相关研究刊登于国际杂志Scientific Reports上。文章中研究者发现，恢复胰腺癌间质细胞中microRNA-29的功能或可有效抑制癌细胞的活力和生长。
  围绕在癌细胞周围较厚的纤维壳被认为是子座，其可以保护胰腺癌细胞免于抗癌药物比如化疗药物的攻击作用；研究者Kota博士指出，miR-29的缺失在胰腺癌细胞中非常普遍，而利用miR-29作为一种治疗性的靶点或将开发出胰腺癌的特效疗法，因为单一的miRNA可以调节和疾病发病机制相关的多种基因的表达。
  在健康细胞和组织中，单一的miRNA可以控制成千上万个基因的表达，而且基因正常表达的任何改变都会导致引发癌细胞无限增殖的有害基因的过量表达，同时这对健康细胞也是有害的。文章中研究者主要对小型非编码RNAs（miRNAs）进行了研究，这些miRNAs的分子机制同胰腺癌子座（间质）的发生直接相关，研究者希望通过该研究可以评估利用miRNAs治疗干预胰腺癌的作用。
  研究者发现，相比健康胰腺组织而言，miR-29在胰腺肿瘤中是缺失的，而且研究者希望miR-29在间质细胞中的表达可以帮助恢复间质细胞的正常功能以及纤维间质蛋白的含量；然而研究者还发现，当将过表达miR-29的间质细胞同癌细胞共同培养时，miR-29会有效抑制癌细胞的活力和生长势头。
  当前还需要进行更多研究来理解间质细胞中miR-29过表达对癌细胞影响相关的分子机制，而miR-29特殊作用的发现或可帮助客服当前许多抗间质细胞药物及其它治疗手段所引发的问题，研究者表示，后期他们将对miR-29进行更多深入的研究，来以其作为基础开发治疗胰腺癌的新型治疗手段。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Pathophysiological role of microRNA-29 in pancreatic cancer stroma
Scientific Reports      doi:10.1038/srep11450
Jason J. Kwon, Sarah C. Nabinger, Zachary Vega, Smiti Snigdha Sahu, Ravi K. Alluri, Zahi Abdul-Sater, Zhangsheng Yu, Jesse Gore, Grzegorz Nalepa, Romil Saxena, Murray Korc & Janaiah Kota
Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma (PDAC) is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Current, anti-stromal therapies have failed to improve tumor response to chemotherapy and patient survival. Furthermore, recent studies show that stroma impedes tumor progression, and its complete ablation accelerates PDAC progression. In an effort to understand the molecular mechanisms associated with tumor-stromal interactions, using in vitro and in vivo models and PDAC patient biopsies, we show that the loss of miR-29 is a common phenomenon of activated pancreatic stellate cells (PSCs)/fibroblasts, the major stromal cells responsible for fibrotic stromal reaction. Loss of miR-29 is correlated with a significant increase in extracellular matrix (ECM) deposition, a major component in PDAC stroma. Our in vitro miR-29 gain/loss-of-function studies document the role of miR-29 in PSC-mediated ECM stromal protein accumulation. Overexpression of miR-29 in activated stellate cells reduced stromal deposition, cancer cell viability, and cancer growth in co-culture. Furthermore, the loss of miR-29 in TGF-β1 activated PSCs is SMAD3 dependent. These results provide insights into the mechanistic role of miR-29 in PDAC stroma and its potential use as a therapeutic agent to target PDAC.