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

Abstract

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-of-function 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.