Research Paper Volume 11, Issue 17 pp 6734—6761
MicroRNA-330-3p promotes brain metastasis and epithelial-mesenchymal transition via GRIA3 in non-small cell lung cancer
- 1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2 Medical Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 3 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Received: February 14, 2019 Accepted: August 12, 2019 Published: September 8, 2019
https://doi.org/10.18632/aging.102201How to Cite
Copyright © 2019 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to identify microRNAs (miRNAs) that could serve as biomarkers to differentiate NSCLC patients with and without BM. Logistic regression was conducted with 122 NSCLC patients (60 without BM, 62 with BM) to assess the association between miRNAs and BM. We confirmed several risk factors for BM and revealed that serum miR-330-3p levels are higher in NSCLC patients with BM than that without BM. Overexpression of miR-330-3p promoted proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells in vitro and NSCLC tumorigenesis in vivo. Knocking down miR-330-3p suppressed this metastatic phenotype. We identified putative miR-330-3p target genes by comparing mRNA microarray analysis data from A549 cells after miR-330-3p knockdown with candidate miR-330-3p target genes predicted by public bioinformatic tools and luciferase reporter assays. We found that GRIA3 is a target of miR-330-3p and that miR-330-3p stimulates EMT progress by mediating GRIA3-TGF-β1 interaction. Our results provide novel insight into the role of miR-330-3p in NSCLC metastasis, and suggest miR-330-3p may be a useful biomarker for identifying NSCLC with metastatic potential.