Circ_0014130 is involved in the drug sensitivity of colorectal cancer through miR-197-3p/PFKFB3 axis.

Background And Aim: Colorectal cancer (CRC) is one of the most deadly cancers in the world, with few treatments and a poor prognosis. In recent years, many circular RNAs have been studied in CRC, but the role of circ_0014130 in CRC has not been investigated. Therefore, this research is designed to investigate the impact of circ_0014130 on the resistance of 5-fluorouracil (5-FU) in CRC.

Methods: Quantitative real-time polymerase chain reaction was conducted to assess the expression of circ_0014130, microRNA-197-3p (miR-197-3p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3). The expression of PFKFB3 protein was detected by Western blot. The effect of cric_0014130 on drug resistance in CRC was verified by Cell Counting Kit-8 assay, clone formation assay, Transwell, and flow cytometry. The effect of circ_0014130 on tumor growth was evaluated by xenograft tumor model in vivo.

Results: Circ_0014130 and PFKFB3 were increased, while miR-197-3p was reversed in CRC tissues and cells. Knocking down circ_0014130 can promote cell apoptosis, inhibit the proliferation of CRC cells, and reduced the IC50 of 5-FU. In addition, miR-197-3p inhibitors reversed the effect of si-circ_0014130 on CRC cells. Similarly, overexpression of PFKFB3 can regulate CRC cell behavior and 5-FU resistance caused by miR-197-3p. Finally, decrease of circ_0014130 was demonstrated to enhance the resistance of 5-FU in CRC tissues in vivo.

Conclusion: Circ_0014130 modulates 5-FU resistance in CRC by modulating the miR-197-3p/PFKFB3 axis, which is helpful for drug chemotherapy in CRC.