LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer

被引:74
|
作者
Gong, Pihai [1 ,2 ]
Qiao, Fengchang [1 ,2 ]
Wu, Huazhang [1 ,2 ]
Cui, He [1 ,2 ]
Li, Yiping [3 ]
Zheng, Ying [1 ,2 ]
Zhou, Menghan [1 ,2 ]
Fan, Hong [1 ]
机构
[1] Southeast Univ, Minist Educ, Key Lab Dev Genes & Human Dis, Dept Med Genet & Dev Biol,Med Sch, Nanjing, Jiangsu, Peoples R China
[2] Southeast Univ, Sch Life Sci, Nanjing, Jiangsu, Peoples R China
[3] Southeast Univ, Med Sch, Dept Pathophysiol, Nanjing, Jiangsu, Peoples R China
来源
CELL DEATH & DISEASE | 2018年 / 9卷
基金
中国国家自然科学基金;
关键词
NONCODING RNA UCA1; CARDIOMYOCYTE APOPTOSIS; CELL-PROLIFERATION; LONG; CARCINOMA; INVASION; EZH2; PROGRESSION; MIGRATION; ZEB2;
D O I
10.1038/s41419-018-1170-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that UCA1 was aberrantly elevated in gastric cancer tissues, and was significantly associated with lymph node metastasis and TNM stage. In vivo and in vitro, enforced UCA1 level promoted cell migration and invasion of GC cell. Depleted UCA1 expression level attenuated the ability of cell migration and invasion in GC. And then, we detected that expression level of ZEB2, a transcription factor related to tumor metastasis, was regulated by UCA1 in GC cells. miR-203 targets and suppresses to ZEB2 expression. Furthermore, we found that UCA1 could directly interact with miR-203 and lead to the release of miR203-targeted transcripts ZEB2. Herein, we revealed the novel mechanism of UCA1 on regulating metastasis-related gene by sponge regulatory axis during GC metastasis. Our findings indicated that UCA1 plays a critical role in metastatic GC by mediating sponge regulatory axis miR-203/ZEB2. To explore function of UCA1-miR-203-ZEB2 axis may provide an informative biomarker of malignancy and a highly selective anti-GC therapeutic target.
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页数:14
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