Low KIF26B Expression Reduces Paclitaxel Resistance and Predicts Good Prognosis in Ovarian Cancer

TL;DR

Low levels of KIF26B in ovarian cancer cells reduce resistance to paclitaxel and improve patient outcomes, suggesting it could be a new treatment target.

Contribution

This study identifies KIF26B as a novel factor in paclitaxel resistance and prognosis in ovarian cancer.

Findings

KIF26B is highly expressed in ovarian cancer and chemotherapy-resistant tissues.

Reducing KIF26B levels decreases paclitaxel resistance and promotes cancer cell death.

KIF26B interacts with SLC7A11 to influence chemotherapy response and prognosis.

Abstract

Ovarian cancer, the most lethal type of tumour of the female reproductive system, severely threatens women’s life and health. Despite paclitaxel being a key chemotherapeutic agent in the standard treatment for ovarian cancer, the majority of patients eventually develop resistance to paclitaxel, constituting a significant obstacle to successful treatment. KIF26B, a kinesin family protein, is involved in various cancers, but its role in ovarian cancer and chemotherapy resistance is unclear. In this study, we evaluated the role of KIF26B in drug-resistant ovarian cancer and the underlying mechanisms. Bioinformatics analysis revealed that KIF26B was highly expressed in ovarian cancer tissues and was associated with poor clinical characteristics. Moreover, KIF26B expression was consistently high in chemotherapy-resistant tissues across multiple treatment subgroups, with ROC curve analyses confirming its predictive power for chemoresistance, particularly in advanced serous ovarian cancer. To further investigate the role of KIF26B in ovarian cancer resistance, the effects of KIF26B on cell proliferation, colony formation, the cell cycle, apoptosis, and microtubule polymerization under paclitaxel treatment were assessed. KIF26B knockdown significantly reduced paclitaxel resistance in ovarian cancer cells, inhibited cell proliferation, and promoted apoptosis. Furthermore, KIF26B interference induced cell cycle arrest and altered microtubule polymerization dynamics in paclitaxel-resistant cells. Additionally, our analyses revealed a negative correlation between KIF26B and SLC7A11 in ovarian cancer, particularly in chemoresistant tissues. Combined KIF26B and SLC7A11 expression provided stronger prognostic value than either gene alone did, and functional assays demonstrated that SLC7A11 contributed to the regulation of the KIF26B-mediated paclitaxel response. Overall, our results indicate that KIF26B is crucial for ovarian cancer progression and chemotherapy resistance, likely through SLC7A11 regulation. KIF26B may serve as a potential therapeutic target for overcoming paclitaxel resistance.

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