| Literature DB >> 28473531 |
Dongmei Zhang1,2,3, Gao Zhang4,5, Xiaowen Hu2, Lawrence Wu4,5, Yi Feng2, Sidan He6, Youyou Zhang2, Zhongyi Hu2, Lu Yang1,2, Tian Tian7, Weiting Xu7, Zhi Wei7, Yiling Lu8, Keith T Flaherty9, Xiaomin Zhong2,10, Gordon B Mills8, Phyllis A Gimotty6, Xiaowei Xu11, Meenhard Herlyn12,5, Lin Zhang13.
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 Orilnc1 as a genetic target of RAS that is critical for RAS oncogenicity. Orilnc1 expression was regulated by RAS-RAF-MEK-ERK signaling via the transcription factor AP1. Orilnc1 was highly expressed in BRAF-mutant cancers, such as melanoma. Silencing of Orilnc1 blocked tumor cell proliferation and growth in vitro and in vivo In addition, Orilnc1 blockade reduced expression of cyclin E1 and induced G1-S cell-cycle arrest in tumor cells. Taken together, our results identify Orilnc1 as a novel, nonprotein mediator of RAS/RAF activation that may serve as a therapeutic target in RAS/RAF-driven cancers. Cancer Res; 77(14); 3745-57. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28473531 PMCID： PMC5511552 DOI： 10.1158/0008-5472.CAN-16-1768
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701