J Cancer 2018; 9(2):331-345. doi:10.7150/jca.18188

Research Paper

MiR-378 and MiR-1827 Regulate Tumor Invasion, Migration and Angiogenesis in Human Lung Adenocarcinoma by Targeting RBX1 and CRKL, Respectively

Chai San Ho1, Suzita Mohd Noor2, Noor Hasima Nagoor3✉

1. Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia;
2. Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;
3. Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Research in Biotechnology for Agriculture (CEBAR), University of Malaya, 50603 Kuala Lumpur, Malaysia.

Abstract

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 RBX1 and CRKL, 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.

Keywords: MicroRNAs, Lung Cancer, Invasion, Migration, Angiogenesis, EMT.

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How to cite this article:
Ho CS, Noor SM, Nagoor NH. MiR-378 and MiR-1827 Regulate Tumor Invasion, Migration and Angiogenesis in Human Lung Adenocarcinoma by Targeting RBX1 and CRKL, Respectively. J Cancer 2018; 9(2):331-345. doi:10.7150/jca.18188. Available from http://www.jcancer.org/v09p0331.htm