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.
Highlights
Brain metastasis (BM) is the leading cause of poor prognosis, recurrence, and death in patients with nonsmall-cell lung cancer (NSCLC)
Our results provide novel insight into the role of miR-330-3p in non-small cell lung cancer (NSCLC) metastasis, and suggest miR-330-3p may be a useful biomarker for identifying NSCLC with metastatic potential
Our findings indicate that serum and tissue miR-330-3p levels are higher in NSCLC patients with BM than those without BM, and that miR-330-3p may be a useful biomarker for identifying NSCLC with metastatic potential
Summary
Brain metastasis (BM) is the leading cause of poor prognosis, recurrence, and death in patients with nonsmall-cell lung cancer (NSCLC). In nearly 10% of NSCLC patients, BM is already present at diagnosis [1], and develops eventually in 40-55% of these patients [2]. The median overall survival (OS) of NSCLC patients with BM is only 4–6 months after whole brain radiotherapy (WBRT) plus palliative treatment [3]. In patients with limited-stage small-cell lung cancer prophylactic cranial irradiation (PCI) may be of some benefit [4, 5]; the potential effects of PCI in NSCLC remain controversial [6, 7]. MicroRNAs (miRNAs) are a class of conserved small non-coding RNAs 18-25 nucleotides in length [8,9,10]. A single miRNA regulates hundreds of genes [12, 13]
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