Investigating the role of MicroRNA-519d-3p in enhancing chemosensitivity of colorectal cancer cells to 5-Fluorouracil through PFKFB3 targeting

Abstract

Objective: In the fight against Colorectal Cancer (CRC), chemotherapy resistance is a major obstacle. Therefore, it is imperative to identify effective biomarker therapeutics. Despite microRNAs (miRs) playing a crucial role in drug resistance, the mechanisms comprising miR-519d-3p’s role in CRC drug resistance have not been fully understood. Therefore, the present study aimed to investigate the biological function of miR-519d-3p in the chemosensitivity of CRC cells to 5-luorouracil (5-FU). Methods: CRC cells were treated with 5-FU and transfected. Cellular proliferation, invasion, and apoptosis were evaluated. The relationship between miR-519d-3p and 6-Phosphofructokinase-2/Frucose-2, 6-Biphosphatase-3 (PFKFB3) was analyzed, and their interaction in CRC was further investigated. In vivo tumor experiments were conducted to investigate the function of miR-519d-3p and 5-FU in CRC. Results: As determined, CRC cells overexpressing miR-519d-3p were more sensitive to 5-FU in vitro, as miR-519d3p inhibits proliferation and invasion and stimulates apoptosis. miR-519d-3p directly targeted PFKFB3. In CRC cells, PFKFB3 overexpression rescued miR-519d-3p-induced 5-FU toxicity. In vivo results showed that mice cotreated with miR-519d-3p mimics and 5-FU showed higher antitumor activity. Conclusion: Overall, it may be possible to improve 5-FU chemosensitivity of CRC cells by targeting miR-519d-3p and PFKFB3.