Downregulation of miR-145 contributes to lung adenocarcinoma cell growth to form brain metastases

Abstract

The development of metastases involves the dissociation of cells from the primary tumor, penetrating the basement membrane, invasion and exiting from the vasculature to seed, and finally colonizing in distant tissues. The formation of brain metastasis (BM) in lung adenocarcinoma remains poorly understood. We examined the differential microRNA (miRNA) expression profiles of 5 primary and 3 brain metastatic lung adenocarcinoma samples by Agilent miRNA Microarrays. Five upregulated miRNAs (miRs-9*, -1471, 718, 3656, 720) and 3 downregulated miRNAs (miRs-214, -145 and -23a) were detected. The 4 most significantly deregulated miRNAs (miR-145, miR-214, miR-9* and miR-1471) were validated in the additional 43 samples (35 primary and 8 brain metastatic lung adenocarcinoma samples) using TaqMan quantitative PCR. By functional assay, we found that the expression of miR-145 can regulate the ability of proliferation of A549 and SPC-A1 cells in vitro, but is not related to lymph node metastasis, migration and invasion. These results suggest that miR-145 may have a cell type-specific function and play important roles in the process of BM from lung adenocarcinoma.