机构：[1]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou510515, 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.深圳市康宁医院深圳市龙岗区人民医院深圳医学信息中心[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内科片肿瘤内科云南省第一人民医院
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.
基金：
the National Natural Science Funds of China
(grant numbers 81672875 & 81772964), high-level topic-matching funds of Nanfang
Hospital (grant number 201347) and Guangzhou Pilot Project of Clinical and Translational
Research Center (early gastrointestinal cancer, grant number 7415696196402).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou510515, China.
通讯作者：
通讯机构：[1]Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou510515, China.[3]Department of Gastroenterology,Longgang District People’s Hospital, Shenzhen 518172, China.
推荐引用方式(GB/T 7714)：
Tang Weimei,Zhou Weijie,Xiang Li,et al.The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer.[J].Nature communications.2019,10(1):663.doi:10.1038/s41467-018-08225-3.
APA：
Tang Weimei,Zhou Weijie,Xiang Li,Wu Xiaosheng,Zhang Pei...&Wang Jide.(2019).The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer..Nature communications,10,(1)
MLA：
Tang Weimei,et al."The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer.".Nature communications 10..1(2019):663
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