Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer

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 Mills, Phyllis A. Gimotty, Xiaowei Xu, Meenhard Herlyn, Lin Zhang

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 customdesigned 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.

Original languageEnglish (US)
Pages (from-to)3745-3757
Number of pages13
JournalCancer Research
Volume77
Issue number14
DOIs
StatePublished - Jul 15 2017
Externally publishedYes

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Long Noncoding RNA
Neoplasms
Cyclins
Growth
Cell Cycle Checkpoints
Cell Division
Melanoma
Transcription Factors
Cell Proliferation
Genes
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, D., Zhang, G., Hu, X., Wu, L., Feng, Y., He, S., ... Zhang, L. (2017). Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer. Cancer Research, 77(14), 3745-3757. https://doi.org/10.1158/0008-5472.CAN-16-1768

Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer. / Zhang, Dongmei; Zhang, Gao; Hu, Xiaowen; Wu, Lawrence; Feng, Yi; He, Sidan; Zhang, Youyou; Hu, Zhongyi; Yang, Lu; Tian, Tian; Xu, Weiting; Wei, Zhi; Lu, Yiling; Flaherty, Keith T.; Zhong, Xiaomin; Mills, Gordon; Gimotty, Phyllis A.; Xu, Xiaowei; Herlyn, Meenhard; Zhang, Lin.

In: Cancer Research, Vol. 77, No. 14, 15.07.2017, p. 3745-3757.

Research output: Contribution to journalArticle

Zhang, D, Zhang, G, Hu, X, Wu, L, Feng, Y, He, S, Zhang, Y, Hu, Z, Yang, L, Tian, T, Xu, W, Wei, Z, Lu, Y, Flaherty, KT, Zhong, X, Mills, G, Gimotty, PA, Xu, X, Herlyn, M & Zhang, L 2017, 'Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer', Cancer Research, vol. 77, no. 14, pp. 3745-3757. https://doi.org/10.1158/0008-5472.CAN-16-1768
Zhang D, Zhang G, Hu X, Wu L, Feng Y, He S et al. Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer. Cancer Research. 2017 Jul 15;77(14):3745-3757. https://doi.org/10.1158/0008-5472.CAN-16-1768
Zhang, Dongmei ; Zhang, Gao ; Hu, Xiaowen ; Wu, Lawrence ; Feng, Yi ; He, Sidan ; Zhang, Youyou ; Hu, Zhongyi ; Yang, Lu ; Tian, Tian ; Xu, Weiting ; Wei, Zhi ; Lu, Yiling ; Flaherty, Keith T. ; Zhong, Xiaomin ; Mills, Gordon ; Gimotty, Phyllis A. ; Xu, Xiaowei ; Herlyn, Meenhard ; Zhang, Lin. / Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer. In: Cancer Research. 2017 ; Vol. 77, No. 14. pp. 3745-3757.
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AU - Lu, Yiling

AU - Flaherty, Keith T.

AU - Zhong, Xiaomin

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AU - Xu, Xiaowei

AU - Herlyn, Meenhard

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