Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer
Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer
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microRNA-29家族表达的特征及其在胃癌中的作用机制研究。
DOI：
10.1093/carcin/bgt337
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发表时间：
2014-02-01
期刊：
影响因子：
4.7
通讯作者：
Yu, Jia
中科院分区：
文献类型：
--
作者：
Gong, Jianan;Li, Jianxiong;Yu, Jia
越来越多的证据表明microRNAs（miRNAs）的异常表达参与了肿瘤的发生。它们可能成为疾病治疗的新的生物标志物或治疗靶点。miR-29家族在多种癌症中作为肿瘤抑制因子或癌基因发挥作用。然而，其在胃癌中的准确表达、功能和机制尚不清楚。在这里，我们发现miR-29家族成员的表达在GC中与相邻对照相比显著降低。其中，miR-29 c在GC中的百分比降低最多，并且与GC的侵袭性和进行性表型相关。我们进一步证明miR-29家族通过靶向CCND 2和基质金属蛋白酶-2基因在胃癌中发挥肿瘤抑制作用。此外，在患者和异种移植小鼠中证实了miR-29家族与其靶点之间的负相关关系。最后，重新引入miR-29家族显著抑制了异种移植小鼠中GC细胞的肿瘤形成。这些结果揭示了miR-29家族的表达特征，有助于阐明miR-29家族在胃癌中的作用和分子机制，提示miR-29家族可能成为胃癌的新的预后标志物和治疗靶点。
Increasing evidence shows that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. They might be the novel biomarkers or therapeutic targets in disease treatment. miR-29 family was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in gastric cancer (GC) are not well known. Here, we found that the expression of miR-29 family members was significantly reduced in GC compared with adjacent controls. Among them, miR-29c had the most reduced percentage in GC and was associated with aggressive and progressive phenotypes of GC. We further demonstrated that miR-29 family acted as tumor suppressors through targeting CCND2 and matrix metalloproteinase-2 genes in GC. Moreover, the inverse relationship between miR-29 family and their targets was verified in patients and xenograft mice. Finally, reintroduction of miR-29 family significantly inhibited tumor formation of GC cells in the xenograft mice. Take together, our finding characterized the expression properties of miR-29 family, contributed to the function and molecular mechanism of miR-29 family in GC and implied that miR-29 family might be employed as novel prognostic markers and therapeutic targets of GC.