FBXO17 regulates the malignant progression of colorectal cancer via the Wnt/β-catenin pathway.

BACKGROUND

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, often presenting without apparent early symptoms, and most patients are diagnosed at an advanced stage with a poor prognosis. F-box protein 17 (FBXO17) is up-regulated in various tumors and may represent a potential prognostic marker in CRC. This study sought to elucidate FBXO17's specific role in CRC and the underlying mechanism.

METHODS

Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), together with Western blot, was applied to determine FBXO17 expression in CRC cell lines. FBXO17-silenced and FBXO17-overexpressing CRC cells were established using a lentiviral system and liposome transfection technology, respectively. Cell counting kit-8, Transwell, and wound healing assays, as well as Western blot, were used to assess CRC cell proliferation, invasion, and migration, and to examine Wnt/β-catenin pathway activation. Intracellular reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), oxidized glutathione, and reduced glutathione, along with GPX4 and PTGS2 protein expression, were determined to assess CRC cell ferroptosis.

RESULTS

Compared with human normal colon cells, human CRC cells exhibited generally high FBXO17 expression. Silencing FBXO17 led to decreased CRC cell proliferation, invasion, and migration, attenuated Wnt/β-catenin pathway activation, and enhanced ferroptosis, whereas overexpression of FBXO17 reversed these effects by enhancing CRC cell proliferation, invasion, and migration, activating the Wnt/β-catenin pathway, and suppressing ferroptosis. Furthermore, treatment with ferrostatin-1 (ferroptosis inhibitor) or CHIR-99021 (Wnt/β-catenin pathway agonist) enhanced the proliferation, invasion, and migration of FBXO17-silenced CRC cells while attenuating ferroptosis.

CONCLUSIONS

Silencing FBXO17 can promote CRC cell ferroptosis but inhibit proliferation, invasion, and migration through suppression of Wnt/β-catenin pathway activation.