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The long noncoding RNA SNHG1 promotes tumor growth through regulating transcription of both local and distal genes

Oncogene volume 36, pages 6774–6783 (2017)Cite this article

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Abstract

Increasing evidence indicates that long noncoding RNAs (lncRNAs) have important roles in various physiological processes and dysfunction of lncRNAs could be a prevalent cause in human diseases. Here we functionally characterized the nuclear-enriched lncRNA SNHG1, which is highly expressed in multiple types of cancer. We also provide evidence that SNHG1 promotes cancer cell growth by regulating gene expression both in cis and in trans. SNHG1 was involved in the AKT signaling pathway as it promotes the neighboring transcription of the protein-coding gene SLC3A2 in cis by binding the Mediator complex to facilitate the establishment of enhancer–promoter interaction. In trans, SNHG1 directly interacted with central domain of FUBP1 and antagonize the binding of FBP-interacting repressor to FUBP1, thereby coordinating the expression of the oncogene MYC. Collectively, our findings demonstrate that lncRNA SNHG1 can function both in cis and in trans with distinct mechanisms to regulate transcription, promoting tumorigenesis and cancer progression.

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Acknowledgements

We thank Professor Zushen Fan, Dr Greta Pintacuda and Dr Tianyi Zhang for helpful suggestions and critical reading of this manuscript and Professors Yajun Guo and Mingzhou Guo of Chinese PLA General Hospital and Youyong Lu of Peking University Cancer Hospital and Institute for kindly providing clinical samples. We also thank Dr Junbing Wu, Dongpeng Wang, Shuheng Wu and Bao Zhang for helping with animal experiments. This work was supported by grants from the National Natural Science Foundation of China (31520103905, 31401098) and the National High Technology Research and Development Program (‘863’ Program of China) 2015AA020108. The raw sequencing data reported in this work have been deposited in GEO (GSE85842).

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Author notes

  1. Y Sun, G Wei, H Luo and W Wu: These authors are co-first authors.

Authors and Affiliations

  1. Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    Y Sun, G Wei, H Luo, W Wu, G Skogerbø, J Luo & R Chen

  2. Department of Biochemistry, University of Oxford, Oxford, UK

    G Wei

  3. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

    W Wu

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  1. Y Sun
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Correspondence to R Chen.

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Sun, Y., Wei, G., Luo, H. et al. The long noncoding RNA SNHG1 promotes tumor growth through regulating transcription of both local and distal genes. Oncogene 36, 6774–6783 (2017). https://doi.org/10.1038/onc.2017.286

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