Research Paper Volume 10, Issue 12 pp 3662—3682

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

Liang Wang 1, *, , Zhewei Wei 1, *, , Kaiming Wu 1, , Weigang Dai 1, , Changhua Zhang 1, , Jianjun Peng 1, , Yulong He 1, ,

  • 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
* Equal contribution

received: August 28, 2018 ; accepted: October 27, 2018 ; published: December 10, 2018 ;

https://doi.org/10.18632/aging.101628
How to Cite

Copyright: Wang et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

lncRNAs: long noncoding RNAs; miR-203: microRNA-203; EMT: epithelial-to-mesenchymal transition; MET: mesenchymal-to-epithelial transition; miRNA: microRNA; qRT-PCR: quantitative real-time PCR; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; EdU: Ethynyl deoxyuridine; ChIRP: chromatin isolation by RNA purification; HE: hematoxylin-eosin.