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

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, Jing Xiong, Chen Ye, Aimin Li (), Side Liu () and Jide Wang ()
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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
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
Jide Wang: Southern Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08225-3

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