Jiang Kanqiu, Zhao Ting, Shen Mingjing, Zhang Fuquan, Duan Shanzhou, Lei Zhe, Chen Yongbing
Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou 215004, China.
Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China.
J Cancer. 2019 Jun 2;10(12):2735-2744. doi: 10.7150/jca.31800. eCollection 2019.
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.
越来越多的证据表明，miR-940可抑制癌细胞的迁移和侵袭。鉴于转化生长因子β（TGF-β）信号传导对细胞上皮-间质转化（EMT）过程及癌症转移至关重要，因此迫切需要探究miR-940在肺癌进展过程中是否以及如何在调节TGF-β诱导的EMT中发挥重要作用。在本研究中，我们观察到在非小细胞肺癌（NSCLC）组织中miR-940表达下调而Snail mRNA表达上调，二者呈反向表达。我们进一步发现，在伴有淋巴结转移、TNM分期较晚及细胞分化差的NSCLC组织中，miR-940的表达降低，而相反，Snail的表达增加。miR-940过表达显著抑制了A549和H226细胞中Snail mRNA和蛋白的表达。从机制上来说，Snail mRNA被确定为miR-940的靶标。此外，miR-940抑制了TGF-β诱导的EMT，并进一步阻碍了细胞的迁移和侵袭。最后，siRNA介导的Snail基因敲低在A549和H226细胞中复制了miR-940过表达的表型。综上所述，我们的研究表明，miR-940可通过靶向NSCLC中Snail的3'-UTR mRNA来抑制TGF-β诱导的EMT和细胞侵袭。
