Circular RNA‑MTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis

: Circular RNAs (circRNAs), a class of endogenous RNAs, have emerged as an enigmatic class of genes. However, little is known about their value in the progression and chemoresistance of cancers. The present study sought to determine the expression profiles and potential modulatory role of circRNAs on breast cancer cell viability and monastrol resistance. Monastrol-resistant cell lines were established by exposing breast cancer cells to increasing concentrations of monastrol. A human circRNA microarray was used to search for dysregulated circRNAs in monastrol-resistant cells, then circRNA‑MTO1 (hsa‑circRNA-007874) was validated as a circRNA that exhibited elevated expression levels in monastrol-resistant cells. Mechanistic investigations suggested that upregulation of circRNA‑MTO1 suppressed cell viability, promoted monastrol-induced cell cytotoxicity and reversed monastrol resistance. Subsequently, Eg5 was identified as the functional target of circRNA‑MTO1, and MTO1 inhibited Eg5 protein level but not mRNA level. By treating with protein synthesis inhibitor cycloheximide (CHX), it was revealed that MTO1 did not affect the protein stability of Eg5. RNA-pull down experiments followed by mass spectrometry revealed that MTO1 interacted with tumor necrosis factor receptor associated factor 4 (TRAF4), and sequester TRAF4 from activating Eg5 translation, thereby inhibiting the Eg5 protein level. Taken together, the data reveal a regulatory mechanism by circRNA‑MTO1 to control cell viability and monastrol resistance in breast cancer cells.