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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

Chunhua Wei1, Ruiguang Zhang1, Qian Cai1, Xican Gao1, Fan Tong1, Jihua Dong2, Yu Hu3, Gang Wu1, Xiaorong Dong1
  • 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 2Medical Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
* Equal contribution
Received: February 14, 2019Accepted: August 12, 2019Published: September 8, 2019
https://doi.org/10.18632/aging.102201

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.