首页> 外文期刊>Journal of Cancer >MiR-940 inhibits TGF-β-induced epithelial-mesenchymal transition and cell invasion by targeting Snail in non-small cell lung cancer
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MiR-940 inhibits TGF-β-induced epithelial-mesenchymal transition and cell invasion by targeting Snail in non-small cell lung cancer

机译:MiR-940通过靶向Snail抑制非小细胞肺癌TGF-β诱导的上皮-间质转化和细胞侵袭

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Increased evidence reveals that miR-940 inhibits the migration and invasion of cancer cells. Considering transforming growth factor β (TGF-β) signaling is crucial to cellular epithelial-mesenchymal transition (EMT) process and metastasis of cancer, it is in urgent to explore whether and how miR-940 plays an essential role in regulating TGF-β-induced EMT in lung cancer progression. In the present study, we observed a reciprocal expression with down-regulated miR-940 and up-regulated Snail mRNA in non-small-cell lung cancer (NSCLC) tissues. we further found that the expression of miR-940 was decreased in NSCLC tissues with lymph node metastasis, advanced TNM stages and poor cell differentiation, in which, on the contrary, the expression of Snail was increased. Overexpression of miR-940 significantly inhibited Snail mRNA and protein expression in A549 and H226 cells. Mechanistically, Snail mRNA was identified as target of miR-940. In addition, miR-940 repressed TGF-β-induced EMT and further hampered the cell migration and invasion. Finally, siRNA-mediated knockdown of Snail copied the phenotype of miR-940 overexpression in A549 and H226 cells. Taken together, our study reveals that miR-940 can suppress TGF-β-induced EMT and cell invasion by targeting Snail 3'-UTR mRNA in NSCLC.
机译:越来越多的证据表明,miR-940可抑制癌细胞的迁移和侵袭。考虑到转化生长因子β(TGF-β)信号对于细胞上皮-间质转化(EMT)过程和癌症转移至关重要,因此迫切需要探索miR-940是否以及如何在调节TGF-β-中起重要作用诱发EMT在肺癌进展中的作用。在本研究中,我们观察到非小细胞肺癌(NSCLC)组织中miR-940的下调和Snail mRNA的上调表达。我们进一步发现在淋巴结转移,TNM晚期和细胞分化较差的NSCLC组织中,miR-940的表达降低,相反,Snail的表达增加。 miR-940的过表达显着抑制A549和H226细胞中Snail mRNA和蛋白表达。从机理上讲,Snail mRNA被鉴定为miR-940的靶标。此外,miR-940抑制TGF-β诱导的EMT,并进一步阻碍细胞迁移和侵袭。最后,siRNA介导的Snail的敲除复制了A549和H226细胞中miR-940过表达的表型。两者合计,我们的研究表明,miR-940可通过靶向NSCLC中的Snail 3'-UTR mRNA来抑制TGF-β诱导的EMT和细胞侵袭。

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