Abnormal expression of kinesins has been observed in several types of cancer. The present study provided the first evidence that KIF26B could induce RNA m 5 C modification in bladder cancer (BCa). Detailly, KIF26B interacted with NSUN2 and recruited ubiquitinase STUB1 to promote K63-linked ubiquitination of NSUN2 at K511 site. K63-linked ubiquitination enabled NSUN2 to bind to KPNA1 and translocate into nucleus where it drove RNA m 5 C modification. Furthermore, KIF26B induced liquid-liquid phase separation (LLPS) of YBX1 and upregulated IL-6 expression through NSUN2/m 5 C/YBX1 axis. Secreted IL-6 then activated STAT3 signaling to promote transcription of kif26b through direct binding between STAT3 and kif26b promoter. IL-6 also recruited DLAT to acetylate NSUN2 at K229 site and increased association affinity between NSUN2 and KIF26B. Together, these established a KIF26B/NSUN2/m 5 C/IL-6 positive feedback loop, suggesting that targeting KIF26B may be a promising therapeutic strategy for BCa.
Wang et al. (Mon,) studied this question.