Abstract
5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in the treatment of colon cancer. However, acquired chemoresistance is becoming one of the major challenges for patients with advanced stages of colon cancer. Currently, the mechanisms underlying cancer cell resistance to 5-FU are not fully understood. MicroRNAs (miRNA) have been suggested to play important roles in tumorigenesis and drug resistance in colon cancer. In this study, we generated 5-FU-resistant colon cancer cell lines from which we found that miR-122 was downregulated in 5-FU-resistant cells compared with sensitive cells. Meanwhile, the glucose metabolism is significantly upregulated in 5-FU-resistant cells. We report that PKM2 is a direct target of miR-122 in colon cancer cell. Importantly, overexpression of miR-122 in 5-FU-resistant cells resensitizes 5-FU resistance through the inhibition of PKM2 both in vitro and in vivo. In summary, these findings reveal that the dysregulated glucose metabolism contributes to 5-FU resistance, and glycolysis inhibition by miR-122 might be a promising therapeutic strategy to overcome 5-FU resistance.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
