Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 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 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.

• Authors: Dongmei Zhang, Gao Zhang, Xiaowen Hu, Lawrence Wu, Yi Feng, Sidan He, Youyou Zhang, Zhongyi Hu, Lu Yang, Tian Tian, Weiting Xu, Zhi Wei, Yiling Lu, Keith T Flaherty, Xiaomin Zhong, Gordon B Mills, Phyllis A Gimotty, Xiaowei Xu, Meenhard Herlyn, Lin Zhang
• Journal: Cancer research (Cancer Res) Vol. 77 Issue 14 Pg. 3745-3757 (07 15 2017) ISSN: 1538-7445 [Electronic] United States
• PMID: 28473531 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• RNA, Long Noncoding

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Female
• Genes, ras
• Heterografts
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Mice
• Mice, Nude
• Neoplasms (genetics)
• RNA, Long Noncoding (genetics)
• Signal Transduction