The Oncogenic Role of microRNA-130a/301a/454 in Human Colorectal Cancer via Targeting Smad4 Expression
The Oncogenic Role of microRNA-130a/301a/454 in Human Colorectal Cancer via Targeting Smad4 Expression
复制标题
microRNA-130a/301a/454通过靶向Smad4表达在人结直肠癌中的致癌作用
DOI：
10.1371/journal.pone.0055532
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发表时间：
2013-02-05
期刊：
影响因子：
3.7
通讯作者：
Han, Weidong
中科院分区：
文献类型：
--
作者：
Liu, Lin;Nie, Jing;Han, Weidong
转化生长因子（TGF）-β/Smad信号在结肠癌的发生、发展和转移中起重要作用。在这项研究中，我们证明了microRNA-130 a/301 a/454家族在结肠癌组织中与配对的相邻正常粘膜相比上调，其共享相同的3 '-非翻译区（3'-UTR）结合种子序列，并被预测为靶向Smad 4。在结肠直肠癌HCT 116和SW 480细胞中，miRNA-130 a/301 a/454模拟物的过表达增强了细胞增殖和迁移，而这些miRNA的抑制剂影响细胞存活。miRNA-130 a/301 a/454对结肠癌细胞的生物学功能可能是通过抑制Smad 4介导的，并且在人类结肠癌中miRNA的上调与Smad 4的下调相关。总之，这些结果表明，miRNA-130 a/301 a/454是通过调节TGF-β/Smad信号通路促进结肠肿瘤发生的新的致癌miRNA，其可能在癌症治疗中具有潜在的应用。
Transforming growth factor (TGF)-beta/Smad signaling plays an important role in colon cancer development, progression and metastasis. In this study we demonstrated that the microRNA-130a/301a/454 family is up-regulated in colon cancer tissues compared to paired adjacent normal mucosa, which share the same 3'-untranslational region (3'-UTR) binding seed sequence and are predicated to target Smad4. In colorectal cancer HCT116 and SW480 cells, overexpression of miRNA-130a/301a/454 mimics enhances cell proliferation and migration, while inhibitors of these miRNAs affect cell survival. The biological function of miRNA-130a/301a/454 on colon cancer cells is likely mediated by suppression of Smad4, and the up-regulation of the miRNAs is correlated with Smad4 down-regulation in human colon cancers. Collectively, these results suggest that miRNA-130a/301a/454 are novel oncogenic miRNAs contributing to colon tumorigenesis by regulating TGF-beta/Smad signaling, which may have potential application in cancer therapy.