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The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer

Author

Listed:
  • Weimei Tang

    (Southern Medical University)

  • Weijie Zhou

    (Southern Medical University)

  • Li Xiang

    (Longgang District People’s Hospital)

  • Xiaosheng Wu

    (Southern Medical University)

  • Pei Zhang

    (Southern Medical University
    Liuzhou General Hospital)

  • Jing Wang

    (Southern Medical University)

  • Guangnan Liu

    (Southern Medical University)

  • Wenjing Zhang

    (Kunming University of Science and Technology)

  • Ying Peng

    (Southern Medical University)

  • Xiaoting Huang

    (Southern Medical University)

  • Jianqun Cai

    (Southern Medical University)

  • Yang Bai

    (Southern Medical University)

  • Lan Bai

    (Southern Medical University)

  • Wei Zhu

    (Southern Medical University)

  • Hongxiang Gu

    (Southern Medical University)

  • Jing Xiong

    (Southern Medical University)

  • Chen Ye

    (Southern Medical University)

  • Aimin Li

    (Southern Medical University)

  • Side Liu

    (Southern Medical University
    Longgang District People’s Hospital)

  • Jide Wang

    (Southern Medical University
    Longgang District People’s Hospital)

Abstract

The biological role of miR-500a-5p has not yet been reported in the context of colorectal cancer (CRC). Here, we show that miR-500a-5p expression is decreased in CRC tissues compared with adjacent normal tissues. Low miR-500a-5p expression is associated with malignant progression. Moreover, transfection of CRC cells with miR-500a-5p induces G0/G1 cell cycle arrest and inhibits their growth and migration. Mechanistically, miR-500a-5p directly targets HDAC2 and inhibits HDAC2-mediated proliferation in CRC in nude mice. Furthermore, YY1 binds to the promoter of miR-500a-5p and negatively regulates its transcription. Restoration of miR-500a-5p expression is up-regulated via the p300/YY1/HDAC2 complex. Besides, therapeutic delivery of miR-500a-5p significantly suppresses tumour development in a xenograft tumour model and a HDAC2 inhibitor FK228-treated CRC model. Our studies demonstrate that miR-500a-5p functions as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis, which contributes to the development of and provides new potential candidates for CRC therapy.

Suggested Citation

  • Weimei Tang & Weijie Zhou & Li Xiang & Xiaosheng Wu & Pei Zhang & Jing Wang & Guangnan Liu & Wenjing Zhang & Ying Peng & Xiaoting Huang & Jianqun Cai & Yang Bai & Lan Bai & Wei Zhu & Hongxiang Gu & Ji, 2019. "The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08225-3
    DOI: 10.1038/s41467-018-08225-3
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