Long noncoding RNA LINC00673 epigenetically suppresses KLF4 by interacting with EZH2 and DNMT1 in gastric cancer

被引:46
作者
Ba, Ming-Chen [1 ]
Long, Hui [2 ]
Cui, Shu-Zhong [1 ]
Gong, Yuan-Feng [1 ]
Yan, Zhao-Fei [1 ]
Wu, Yin-Bing [1 ]
Tu, Yi-Nuo [1 ]
机构
[1] Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Intracelom Hypertherm Perfus Therapy Ctr, Guangzhou 510095, Guangdong, Peoples R China
[2] Guangzhou Dermatol Inst, Dept Pharm, Guangzhou 510095, Guangdong, Peoples R China
关键词
long noncoding RNA; LINC00673; DNMT1; EZH2; KLF4; CELL-PROLIFERATION; POOR-PROGNOSIS; PROGRESSION; STATISTICS;
D O I
10.18632/oncotarget.20980
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients. Higher LINC00673 expression predicted poor disease-free survival (DFS) and overall survival (OS) in GC patients. By univariate and multivariate Cox analysis, the results confirmed that higher LINC00673 expression was an independent risk factor of prognosis in patients. Knockdown of endogenous LINC00673 significantly inhibited cell proliferation, colony formation number, cell migration and invasion in GC. Furthermore, knockdown of endogenous LINC00673 reduced the expression levels of PCNA, CyclinD1 and CDK2 in GC cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) proved that LINC00673 suppressed KLF4 expression by interacting with EZH2 and DNMT1 in GC cells. Moreover, we confirmed that LINC00673 promoted cell proliferation and invasion by partly repressing KLF4 expression in GC. Taken together, these results indicated that LINC00673 may be a prognostic biomarker and therapeutic target for GC patients.
引用
收藏
页码:95542 / 95553
页数:12
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