RUNX3 regulates vimentin expression via miR-30a during epithelial-mesenchymal transition in gastric cancer cells.
RUNX3 regulates vimentin expression via miR-30a during epithelial-mesenchymal transition in gastric cancer cells.
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DOI：
10.1111/jcmm.12209
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发表时间：
2014-04
影响因子：
5.3
通讯作者：
Jia J
中科院分区：
文献类型：
--
作者：
Liu Z;Chen L;Zhang X;Xu X;Xing H;Zhang Y;Li W;Yu H;Zeng J;Jia J
Runt-related transcription factor 3（RUNX 3）是一种公认的肿瘤抑制因子，通过调节一系列靶基因的表达而发挥作用。临床研究表明，RUNX 3表达缺失与胃癌进展及预后不良有关，但其机制尚不完全清楚。越来越多的证据表明，上皮间质转化（EMT）在肿瘤的复发和转移中起着重要作用。因此，我们探讨了RUNX 3是否在胃癌的EMT中发挥作用。RUNX 3的敲低促进细胞侵袭并增加人胃癌细胞中间充质标志物波形蛋白的蛋白表达。RUNX 3过表达可抑制胃癌细胞的侵袭能力，降低胃癌细胞vimentin蛋白的表达，抑制胃癌细胞在裸鼠体内的定植。此外，RUNX 3的过表达增加了microRNA-30 a（miR-30 a）的表达，miR-30 a直接靶向vimentin的3′非翻译区，降低其蛋白水平。miR-30 a抑制剂消除了RUNX 3介导的细胞侵袭抑制和波形蛋白下调。因此，RUNX 3通过激活miR-30 a抑制胃癌细胞侵袭和波形蛋白表达。在胃癌患者中，RUNX 3水平与miR-30 a呈正相关，与波形蛋白水平呈负相关。总的来说，我们的数据表明RUNX 3的肿瘤抑制活性的一种新的分子机制。针对RUNX 3通路的有效治疗可能有助于通过抑制EMT来控制胃癌细胞的侵袭和转移。
Runt-related transcription factor 3 (RUNX3) is a putative tumour suppressor via regulating the expression of a series of target genes. Clinical studies demonstrated that loss of RUNX3 expression is associated with gastric cancer progression and poor prognosis, but the underlying mechanism is not entirely clear. Accumulating evidence shows that the epithelial–mesenchymal transition (EMT) plays an important role in cancer relapse and metastasis. Therefore, we addressed whether RUNX3 has a role in the EMT in gastric cancer. Knockdown of RUNX3 promoted cell invasion and increased the protein expression of the mesenchymal marker vimentin in human gastric cancer cells. Overexpression of RUNX3 suppressed cell invasion and decreased the protein expression of vimentin in the cells and inhibited gastric cancer cells colonization in nude mice. Furthermore, overexpression of RUNX3 increased the expression of microRNA-30a (miR-30a), and miR-30a directly targeted the 3′ untranslated region of vimentin and decreased its protein level. miR-30a inhibitor abrogated RUNX3-mediated inhibition of cell invasion and downregulation of vimentin. Thus, RUNX3 suppressed gastric cancer cell invasion and vimentin expression by activating miR-30a. In gastric cancer patients, levels of RUNX3 were positively correlated with miR-30a and negatively associated with the levels of vimentin. Collectively, our data suggest a novel molecular mechanism for the tumour suppressor activity of RUNX3. Effective therapy targeting the RUNX3 pathway may help control gastric cancer cell invasion and metastasis by inhibiting the EMT.
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