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LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription

Author

Listed:
  • Hamed Yari

    (The University of Newcastle)

  • Lei Jin

    (The University of Newcastle)

  • Liu Teng

    (Zhengzhou University)

  • Yufang Wang

    (Sichuan University)

  • Yongyan Wu

    (Shanxi Medical University)

  • Guang Zhi Liu

    (Zhengzhou University)

  • Wei Gao

    (Shanxi Medical University)

  • Jin Liang

    (Shanxi Medical University)

  • Yanfeng Xi

    (Shanxi Medical University)

  • Yu Chen Feng

    (The University of Newcastle)

  • Chunming Zhang

    (Shanxi Medical University)

  • Yuan Yuan Zhang

    (The University of Newcastle)

  • Hessam Tabatabaee

    (The University of Newcastle)

  • Ting La

    (The University of Newcastle)

  • Rui Hong Yang

    (Shanxi Medical University)

  • Fu Hua Wang

    (Shanxi Medical University)

  • Xu Guang Yan

    (The University of Newcastle)

  • Margaret Farrelly

    (The University of Newcastle)

  • Rodney Scott

    (The University of Newcastle)

  • Tao Liu

    (University of New South Wales)

  • Rick F. Thorne

    (The University of Newcastle
    Zhengzhou University)

  • Su Tang Guo

    (Shanxi Medical University)

  • Xu Dong Zhang

    (The University of Newcastle
    Zhengzhou University)

Abstract

Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA–DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.

Suggested Citation

  • Hamed Yari & Lei Jin & Liu Teng & Yufang Wang & Yongyan Wu & Guang Zhi Liu & Wei Gao & Jin Liang & Yanfeng Xi & Yu Chen Feng & Chunming Zhang & Yuan Yuan Zhang & Hessam Tabatabaee & Ting La & Rui Hong, 2019. "LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13313-z
    DOI: 10.1038/s41467-019-13313-z
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