Ho Chai San, Noor Suzita Mohd, Nagoor Noor Hasima
Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
J Cancer. 2018 Jan 1;9(2):331-345. doi: 10.7150/jca.18188. eCollection 2018.
MicroRNAs (miRNAs) have been extensively studied over the decades and have been proposed as potential molecular targets for cancer treatment. Studies have shown that miR-378 participates in numerous biological processes in various cancers; whereas miR-1827 has only been reported in pediatric glioma. The mechanism of how miRNAs modulate lung cancer metastasis remains unclear. Our previous study demonstrated that miR-378 is up-regulated while miR-1827 is down-regulated in high invasive lung cancer sub-cell lines, and their biological functions have been described. Here, we report that miR-378 and miR-1827 modulate lung cancer cell invasion and migration via epithelial-mesenchymal transition (EMT). We also demonstrated that cells treated with miR-378 inhibitors or miR-1827 mimics had reduced number of metastases and ectopic vessels in the zebrafish embryo model. We then showed that miR-378 promoted invasion and miR-1827 suppressed migration by targeting and , respectively. Restored protein expression in miRNA-overexpressed/ miRNA-suppressed cells attenuated the inhibitory/ inducing effect of the miRNA on lung cancer cells. Collectively, our findings highlight that miR-378 and miR-1827 could serve as novel therapeutic targets in lung cancer.
几十年来,微小RNA(miRNA)一直受到广泛研究,并被提议作为癌症治疗的潜在分子靶点。研究表明,miR-378参与多种癌症的众多生物学过程;而miR-1827仅在儿童胶质瘤中被报道过。miRNA如何调节肺癌转移的机制仍不清楚。我们之前的研究表明,在高侵袭性肺癌亚细胞系中miR-378上调而miR-1827下调,并且已经描述了它们的生物学功能。在此,我们报告miR-378和miR-1827通过上皮-间质转化(EMT)调节肺癌细胞的侵袭和迁移。我们还证明,用miR-378抑制剂或miR-1827模拟物处理的细胞在斑马鱼胚胎模型中的转移灶和异位血管数量减少。然后我们表明,miR-378分别通过靶向 和 促进侵袭,而miR-1827抑制迁移。在miRNA过表达/miRNA抑制的细胞中恢复蛋白表达减弱了miRNA对肺癌细胞的抑制/诱导作用。总的来说,我们的研究结果突出表明,miR-378和miR-1827可作为肺癌的新型治疗靶点。