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

Nat Commun. 2019 Feb 08;10(1):663
Weimei Tang 1 , Weijie Zhou 2 , Li Xiang 3 , Xiaosheng Wu 1 , Pei Zhang 4 , Jing Wang 1 , Guangnan Liu 1 , Wenjing Zhang 5 , Ying Peng 1 , Xiaoting Huang 1 , Jianqun Cai 1 , Yang Bai 1 , Lan Bai 1 , Wei Zhu 1 , Hongxiang Gu 1 , Jing Xiong 1 , Chen Ye 1 , Aimin Li 6 , Side Liu 7 , Jide Wang 8
Weimei Tang 1 , Weijie Zhou 2 , Li Xiang 3 , Xiaosheng Wu 1 , Pei Zhang 4 , Jing Wang 1 , Guangnan Liu 1 , Wenjing Zhang 5 , Ying Peng 1 , Xiaoting Huang 1 , Jianqun Cai 1 , Yang Bai 1 , Lan Bai 1 , Wei Zhu 1 , Hongxiang Gu 1 , Jing Xiong 1 , Chen Ye 1 , Aimin Li 6 , Side Liu 7 , Jide Wang 8
+ et al

[No authors listed]

Author information
  • 1 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 2 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 3 Department of Gastroenterology, Longgang District People's Hospital, Shenzhen, 518172, China.
  • 4 Department of Gastroenterology, Liuzhou General Hospital, Liuzhou, Guangxi, 545000, China.
  • 5 Department of Medical Oncology, the First people's Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, 650032, China.
  • 6 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. lam0725@163.com.
  • 7 Department of Gastroenterology, Longgang District People's Hospital, Shenzhen, 518172, China. liuside@163.com.
  • 8 Department of Gastroenterology, Longgang District People's Hospital, Shenzhen, 518172, China. jidewang55@163.com.

摘要

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.

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