Long noncoding RNA B3GALT5-AS1 suppresses colon cancer liver metastasis via repressing microRNA-203

被引：73
作者：
Wang, Liang [1 ]
Wei, Zhewei [1 ]
Wu, Kaiming [1 ]
Dai, Weigang [1 ]
Zhang, Changhua [1 ]
Peng, Jianjun [1 ]
He, Yulong [1 ]
机构：
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou 510080, Guangdong, Peoples R China
来源：
AGING-US | 2018年 / 10卷 / 12期
关键词：
long noncoding RNA; colon cancer; liver metastasis; microRNA; epithelial-to-mesenchymal transition; EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; MIR-200; FAMILY; PROMOTES; PROLIFERATION; PROGRESSION; EXPRESSION; ZEB2; EMT;
D O I：
10.18632/aging.101628
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Long noncoding RNAs (lncRNAs) are implicated in various cancers, including colon cancer. Liver metastasis is the main cause of colon cancer-related death. However, the roles of lncRNAs in colon cancer liver metastasis are still largely unclear. In this study, we identified a novel lncRNA B3GALT5-AS1, which is reduced in colon cancer tissues and further reduced in colon cancer liver metastasis tissues. Reduced expression of B3GALT5-AS1 is associated with liver metastasis and poor outcome of colon cancer patients. Gain-of-function and loss-offunction assays revealed that B3GALT5-AS1 inhibited proliferation but promoted migration and invasion of colon cancer cells. Further investigation revealed that B3GALT5-AS1 directly bound to the promoter of miRNA-203, repressed miR-203 expression, upregulated miR-203 targets ZEB2 and SNAI2, and induced epithelial-to-mesenchymal transition (EMT). In vivo study revealed that B3GALT5-AS1 suppressed colon cancer liver metastasis via its binding on miR-203 promoter and the repression of miR-203. miR-203 is increased and epithelial phenotype is preferred in colon cancer liver metastasis tissues. Collectively, our data revealed the suppressive roles of B3GALT5-AS1/miR-203/EMT regulation axis in colon cancer liver metastasis. Our data suggested that the activating B3GALT5-AS1/miR-203/EMT axis may be potential therapeutic strategy for colon cancer liver metastasis.
引用
收藏
页码：3662 / 3682
页数：21
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