Long intergenic non-protein-coding RNA 01446 facilitates the proliferation and metastasis of gastric cancer cells through interacting with the histone lysine-specific demethylase LSD1

被引:13
|
作者
Lian, Yifan [1 ,2 ]
Yan, Changsheng [1 ,2 ]
Lian, Yikai [3 ]
Yang, Renzhi [2 ]
Chen, Qiongyun [1 ,2 ]
Ma, Dan [1 ,2 ]
Lian, Weibin [4 ]
Liu, Jingjing [1 ,2 ]
Luo, Chengyan [5 ]
Ren, Jianlin [1 ,2 ]
Xu, Hongzhi [1 ,2 ]
机构
[1] Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, Xiamen, Fujian, Peoples R China
[2] Xiamen Univ, Sch Med, Inst Microbial Ecol, Xiamen, Fujian, Peoples R China
[3] Xiamen Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, Xiamen, Fujian, Peoples R China
[4] Fujian Med Univ, Dept Breast Surg, Quanzhou Hosp 1, Quanzhou, Fujian, Peoples R China
[5] Nanjing Med Univ, Affiliated Hosp 1, Dept Gynecol, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
EXPRESSION; LNCRNA;
D O I
10.1038/s41419-020-2729-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. However, its biological functions and specific action mechanism in gastric cancer (GC) are still unclear. In our study, LINC01446 was proved to be markedly upregulated in GC tissues relative to the normal tissues, and positively correlated with the poor survival of GC patients. The multivariate Cox regression model showed that LINC01446 functioned as an independent prognostic factor for the survival of GC patients. Functionally, LINC01446 facilitated the proliferation and metastasis of GC cells. Moreover, RNA-seq analysis demonstrated that LINC01446 knockdown primarily regulated the genes relating to the growth and migration of GC. Mechanistically, LINC01446 could widely interact with histone lysine-specific demethylase LSD1 and recruit LSD1 to the Ras-related dexamethasone-induced 1 (RASD1) promoter, thereby suppressing RASD1 transcription. Overall, these findings suggest that LINC01446/LSD1/RASD1 regulatory axis may provide bona fide targets for anti-GC therapies.
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收藏
页数:16
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