# USP25-driven KIFC1 regulates MYCBP expression and promotes the progression of cervical cancer

## TL;DR

This study identifies a new pathway involving USP25, KIFC1, and MYCBP that promotes cervical cancer progression and suggests KIFC1 as a potential treatment target.

## Contribution

The study reveals a novel USP25/KIFC1/MYCBP signaling axis that drives cervical cancer progression.

## Key findings

- KIFC1 is upregulated in cervical cancer tissues and correlates with poor patient outcomes.
- USP25 stabilizes KIFC1 protein, and their suppression reduces MYCBP levels and malignant cell behavior.
- Reintroducing KIFC1 in USP25-deficient cells restores MYCBP expression, confirming their regulatory relationship.

## Abstract

Cervical cancer (CCa) continues to exhibit high mortality rates, compounded by the scarcity of effective therapeutic targets. This study highlights the significant upregulation of Kinesin Family Member C1 (KIFC1), a member of the kinesin-14 family, in CCa tissues. Elevated KIFC1 expression correlates with poorer prognoses in CCa patients. USP25, a deubiquitinating enzyme, stabilizes KIFC1 protein through deubiquitination, facilitating its accumulation in CCa tissues. Our in vitro and in vivo experiments demonstrate KIFC1’s pivotal role in enhancing tumorigenesis and metastasis of CCa cells. Furthermore, we discovered that KIFC1 expression variability could modulate the levels of MYCBP, a known binding partner of the oncogenic protein c-MYC, which influences tumorigenesis. The suppression of USP25 results in decreased KIFC1 and MYCBP protein levels, independent of mRNA changes. However, reintroducing KIFC1 into USP25-deficient cells restores MYCBP expression levels. Simultaneously, targeting USP25, KIFC1 and MYCBP disrupts the malignant phenotype of CCa cells. Collectively, our findings elucidate the previously unknown functions and mechanisms of the USP25/KIFC1/MYCBP signaling axis in CCa progression, underscoring KIFC1 as a promising therapeutic target for cervical cancer.