Cancer Res 2017 07 4;77(14):3745-3757. Epub 2017 May 4.
Center for Research on Reproduction & Women's Health, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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 as a genetic target of RAS that is critical for RAS oncogenicity. expression was regulated by RAS-RAF-MEK-ERK signaling via the transcription factor AP1. was highly expressed in BRAF-mutant cancers, such as melanoma. Silencing of blocked tumor cell proliferation and growth and In addition, blockade reduced expression of cyclin E1 and induced G-S cell-cycle arrest in tumor cells. Taken together, our results identify as a novel, nonprotein mediator of RAS/RAF activation that may serve as a therapeutic target in RAS/RAF-driven cancers. .