Yang W, et al. Carcinogenesis 2020.
Increasing evidence suggest that long non-coding RNAs (lncRNAs) play critical roles in cancers. However, the expression pattern and underlying mechanisms of lncRNAs in non-small cell lung cancer (NSCLC) remain incompletely understood. In this study, lncRNA microarray was performed to identify differential expressed lncRNAs between pre- and post-operation plasma in NSCLC patients. The expression level of candidate lncRNA in NSCLC tissues, plasma, and cells was determined by qRT-PCR and in situ
hybridization (FISH). The functional roles of lncRNA were assessed in vitro and in vivo. Furthermore, RNA pull-down, RNA immunoprecipitation (RIP), microarray, qRT-PCR, and rescue assays were conducted to explore the mechanism action of lncRNA in NSCLC cells. We identified a novel lncRNA (BRCAT54), which was significantly up-regulated in preoperative plasma, NSCLC tissues, and NSCLC cells, and its higher expression was associated with better prognosis in patients with NSCLC. Overexpression of BRCAT54 inhibited proliferation, migration and activated apoptosis in NSCLC cells. Conversely, knockdown of BRCAT54 reversed the suppressive effects of BRCAT54. Moreover, overexpression of BRCAT54 repressed NSCLC cell growth in vivo. Mechanistically, BRCAT54 directly bound to RPS9. Knockdown of RPS9 substantially reversed the promoting effects of si-BRCAT54 on cell proliferation and enhanced the inhibitive effect of si-BRCAT54 on BRCAT54 expression. In addition, silencing of RPS9 activated JAK-STAT pathway and suppressed calcium signaling pathway gene expressions. This study identified BRCAT54 as a tumor suppressor in NSCLC. Targeting the BRCAT54 and RPS9 feedback loop might be a novel therapeutic strategy for NSCLC.