The long non-coding RNA ENST00000547547 reduces 5-fluorouracil resistance of colorectal cancer cells via competitive binding to microRNA-31

Abstract

Colorectal cancer (CRC) is one of the most common cancers and the third leading cause of cancer-related deaths due to its rapid progression and poor prognosis. 5-Fluorouracil (5-FU)-based chemotherapies are the standard treatment for locally advanced CRC. However, a considerable percentage of CRCs have inherent or acquired 5-FU resistance, which critically impedes clinical outcomes. In the present study, we reported that the expression level ENST00000547547 was downregulated in 5-FU-resistant CRC cells in comparison with the parental cells, While rising with the treatment of 5-FU in parental cells. Overexpression of ENST00000547547 promoted 5-FU-induced cell apoptosis and reduced the chemoresistance of 5-FU in vitro. Moreover, we found that ENST00000547547 was a target of miR-31, as confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Notably, miR-31 was upregulated in 5-FU-resistant CRC cells, and knockdown of miR-31 increased the chemosensitivity of 5-FU-resistant CRC cells. Furthermore, we demonstrated that ENST00000547547 reduced the chemoresistance of 5-FU via competitive binding to miR-31 in 5-FU-resistant CRC cell lines. Collectively, our findings revealed that ENST00000547547 reduced chemoresistance in 5-FU of 5-FU-resistant CRC cells through competitive binding to miR-31 and has the potential to serve as a therapeutic target in CRC patients.