Oncogenic RAS Regulates Long Noncoding RNA in Human Cancer.

Cancer Res

Center for Research on Reproduction & Women's Health, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Published: July 2017

AI Article Synopsis

  • RAS signaling pathways play a key role in promoting cell growth and division by regulating gene transcription, but the role of long noncoding RNAs (lncRNAs) in this process is less understood.
  • Using a specialized lncRNA microarray, researchers identified a specific lncRNA that is a significant target of RAS and is crucial for RAS-linked cancer growth, particularly in BRAF-mutant cancers like melanoma.
  • Blocking this lncRNA led to reduced tumor cell proliferation, decreased levels of cyclin E1, and induced cell-cycle arrest, suggesting it could be a promising therapeutic target in cancers influenced by RAS/RAF signaling.

Article 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 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. .

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511552PMC
http://dx.doi.org/10.1158/0008-5472.CAN-16-1768DOI Listing

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