Regulation of MALAT1 expression by TDP43 controls the migration and invasion of non-small cell lung cancer cells in vitro

MALAT1 is a non-coding RNA overexpressed in non-small cell lung cancer (NSCLC). TDP-43 is a ubiquitously expressed, MALAT1-binding protein implicated in cancer development. We hypothesized that MALAT1 expression level is regulated in lung cancer by TDP-43. We analyzed their functions in cultured NSCLC cells. Downregulation of MALAT1 or TDP-43 expression by siRNA not only markedly suppressed NSCLC cell growth, as measured by the MTT assay in vitro cultured NSCLC cells (P < 0.05), but also noticeably impaired the migration and invasion of NSCLC cells, as analyzed by the migration and invasion assay. We also confirm that TDP-43 directly bound to MALAT1 RNA by a RNA immunoprecipitation (RIP) assay and by luciferase reporter activity assay. In a RT-PCR assay, silencing TDP-43 expression effectively decreased MALAT1 RNA transcript level. In contrast, TDP-43 overexpression markedly increased MALAT1 transcript level. In summary, these findings demonstrated that MALAT1 expression by regulation of TDP-43 controls cellular growth, migration, and invasion of NSCLCs. (C) 2015 Elsevier Inc. All rights reserved.