Oncogenic RAS Regulates Long Noncoding RNA <i>Orilnc1</i> in Human Cancer.

Abstract

RAS and its downstream cascades transmit cellular signals, resulting in increased transcription of genes involved in cell growth and division. Protein-coding gene targets of RAS signaling have been characterized extensively, but long noncoding RNAs (lncRNA) regulated by these processes have not. Using a custom-designed lncRNA microarray, we identified the lncRNA <i>Orilnc1</i> as a genetic target of RAS that is critical for RAS oncogenicity. <i>Orilnc1</i> expression was regulated by RAS-RAF-MEK-ERK signaling via the transcription factor AP1. <i>Orilnc1</i> was highly expressed in BRAF-mutant cancers, such as melanoma. Silencing of <i>Orilnc1</i> blocked tumor cell proliferation and growth <i>in vitro</i> and <i>in vivo</i> In addition, <i>Orilnc1</i> blockade reduced expression of cyclin E1 and induced G₁-S cell-cycle arrest in tumor cells. Taken together, our results identify <i>Orilnc1</i> as a novel, nonprotein mediator of RAS/RAF activation that may serve as a therapeutic target in RAS/RAF-driven cancers. <i>Cancer Res; 77(14); 3745-57. ©2017 AACR</i>.