miR-325-3p regulates the development of brain metastases in non-small cell lung cancer through targeting CCL19 gene
Objective:To investigate the molecular mechanisms involved in brain metastases in patients with non-small-cell lung carcinoma.Methods:Two independent data sources(GEO public database and clinical non-small-cell lung carcinoma patient samples)were used to identify the most significant differentially expressed genes and miRNAs.Quantitative PCR was performed to detect the difference between patients with and without brain metastases from non-small-cell lung carcinoma.Using A549 cell line,the effects of target genes on proliferation,differentiation,apoptosis as well as invasion of lung cancer cells,and further investigated the downstream molecular pathways was examined.Results:Compared with patients with non-small cell lung cancer without brain metastases,patients with brain metastases from non-small cell lung cancer demonstrated 352 differentially expressed genes,of which CCL19 gene was the most significant one(low expression,P<0.01).CCL19 was the direct target of miR-325-3p.Luciferase reporter could confirm that miR325-3p directly regulated the expression activity of CCL19.After miR-325-3p inhibitor transfection,the invasion,proliferation and colony formation of A549 cells were significantly reduced(P<0.05),while the level of apoptosis was dramatically increased.At the same time,transfection of CCL19 siRNA could effectively attenuate the effects of miR-325-3p.Meanwhile,this study also implied that CCL19 mainly affected the phosphorylation level of Erk signaling for lung cancer cell functions.Conclusion:As an oncogene,regulated the function of CCL19,and then affected downstream Erk molecular signals,and ultimately manipulated the invasion,proliferation and colony formation of lung cancer cells.
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