LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness

被引：48
|
作者：
Zhu, Yihao [1 ]
Hu, Hanqing [1 ]
Yuan, Ziming [1 ]
Zhang, Qian [1 ]
Xiong, Huan [1 ]
Hu, Zhiqiao [1 ]
Wu, Hongyu [1 ]
Huang, Rui [1 ]
Wang, Guiyu [1 ]
Tang, Qingchao [1 ]
机构：
[1] Harbin Med Univ, Dept Colorectal Surg, Affiliated Hosp 2, Harbin, Peoples R China
来源：
CELL DEATH & DISEASE | 2020年 / 11卷 / 11期
关键词：
CELLS;
D O I：
10.1038/s41419-020-03164-8
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Resistance of chemotherapy is one of causes of recurrence and poor prognosis in patients with colorectal cancer (CRC). The role of differentially expressed long non-coding RNA (lncRNA) in 5-fluorouracil (5-Fu) resistance has not been fully elucidated. Here we observed that lncRNA NEAT1 was associated with 5-Fu resistance in CRC. Our Functional studies showed that NEAT1 promoted 5-Fu resistance in colorectal cells. In addition, A-TAC sequencing and chromatin immunoprecipitation (ChIP) showed that NEAT1 affected chromatin remodeling, increased the acetylation levels of histones, increased their enrichment at the promoters of ALDH1 and c-Myc, and promoted the expression of ALDH1 and c-Myc. Taken together, our study suggested that NEAT1 promoted 5-Fu resistance and cancer stemness by remodeling chromatin. Our finding provides a novel role of NEAT1 and may provide a new strategy for the treatment of CRC 5-Fu resistance.
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页数：11
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