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.
Highlights
Colon cancer is one of the most prevalent malignancies and causes of cancer-related deaths worldwide [1]
In this study, using public available RNA-seq dataset of colon cancer [53], we identified that Long noncoding RNAs (lncRNAs) B3GALT5-AS1 is reduced in colon cancer tissues, and further reduced in colon cancer liver metastasis tissues
Analyzing the RNA-seq dataset from GSE50760 which containing 18 normal colonic epithelium, 18 primary colorectal cancers, and 18 metastasized cancers in liver, we noted that lncRNA B3GALT5-AS1 (C21orf88) is reduced in primary colorectal cancers compared with normal colonic epithelium and is further reduced in metastasized cancers in liver (Fig. 1A)
Summary
Colon cancer is one of the most prevalent malignancies and causes of cancer-related deaths worldwide [1]. Especially liver metastasis accounts for the major cause of deaths of colon cancer patients [2]. Most colon cancer patients with liver metastasis are not suitable for surgery [3]. There is a lack of effective treatments for colon cancer patients with liver metastasis [4]. The prognoses of colon cancers with liver metastases are very poor with a 5year survival rate of 10-15% [5]. Further revealing critical molecular mechanisms driving colon cancer liver metastasis and developing more effective therapies for colon cancers with liver metastasis are urgently needed
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