Qin Qin, Wei Furong, Zhang Jianbo, Li Baosheng
Department of Radiation Oncology (Chest Section), Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong 250117, P.R. China.
Institute of Basic Medicine, Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, University of Jinan‑Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
Oncol Rep. 2017 Feb;37(2):823-830. doi: 10.3892/or.2017.5350. Epub 2017 Jan 3.
Most cancer-related deaths are caused by the development of metastatic disease. Thus, investigation of the underlying mechanisms of metastasis is urgent to design more effective targeted drugs and to treat metastatic disease more effectively. MicroRNAs (miRNAs) have emerged as potential targets for cancer treatment. In the present study, we aimed to identify the roles of miR-134 in non-small cell lung cancer (NSCLC) cell migration and invasion. We demonstrated that overexpression of miR-134 inhibited migration and invasion of A549 and H1299 cells. Further mechanistic investigations revealed that miR-134 inhibited epithelial-to-mesenchymal transition (EMT) evidenced by upregulation of E-cadherin expression and downregulation of vimentin expression. Using luciferase assays, we identified integrin β1 (ITGB1) as a direct target of miR-134. Performing RNAi and rescue experiments, we confirmed that miR-134 exerted its migratory and invasive suppressive role partly by downregulating ITGB1. Finally, an in vivo experiment also, to some extent, suggested that miR-134 may function as a suppressor of metastasis. Taken together, our findings suggest that miR-134 suppresses migration and invasion of NSCLC by targeting ITGB1.
大多数癌症相关死亡是由转移性疾病的发展所致。因此，迫切需要研究转移的潜在机制，以设计出更有效的靶向药物并更有效地治疗转移性疾病。微小RNA（miRNA）已成为癌症治疗的潜在靶点。在本研究中，我们旨在确定miR-134在非小细胞肺癌（NSCLC）细胞迁移和侵袭中的作用。我们证明，miR-134的过表达抑制了A549和H1299细胞的迁移和侵袭。进一步的机制研究表明，miR-134抑制上皮-间质转化（EMT），表现为E-钙黏蛋白表达上调和波形蛋白表达下调。通过荧光素酶测定，我们确定整合素β1（ITGB1）是miR-134的直接靶点。进行RNA干扰和拯救实验后，我们证实miR-134部分通过下调ITGB1发挥其迁移和侵袭抑制作用。最后，一项体内实验在一定程度上也表明，miR-134可能作为转移的抑制因子发挥作用。综上所述，我们的研究结果表明，miR-134通过靶向ITGB1抑制NSCLC的迁移和侵袭。
