Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer

Dysregulation of mitotic processes can induce chromosome instability, which results in aneuploidy, tumorigenesis, and chemo-resistance. Thyroid hormone receptor interactor 13 (TRIP13) is a critical mitosis regulator, and recent studies suggest that it functions as an oncogene in multiple cancers. However, the role of TRIP13 in bladder cancer (BC) is still unknown. In this study, our analysis of RNA-sequencing data from the Cancer Genome Atlas and Gene expression profiling databases showed that TRIP13 expression was upregulated in BC tissues, and overexpression of TRIP13 was significantly associated with poor prognosis of BC patients. In addition, we found a remarkable elevation of TRIP13 in BC samples compared to normal controls by immunohistochemistry. Furthermore, our in vitro functional assays showed that overexpression of TRIP13 promoted the growth/viability, colony formation ability by inducing cell cycle arrest in G2/M phase, as well as enhancing drug resistance of BC cells to cisplatin and doxorubicin. Conversely, knockdown of TRIP13 inhibited cell growth and induced apoptosis of BC cells. Furthermore, TRIP13 acted as an oncogene in BC by inhibiting spindle assembly checkpoint signaling by targeting mitotic arrest deficient 2 (MAD2) protein. TRIP13 overexpression also alleviated cisplatin- and doxorubicin-induced DNA damage and enhanced DNA repair as evidenced by the reduced expression of γH2AX and enhanced expression of RAD50 in drug-treated BC cells. In conclusion, TRIP13 may be a novel target for the treatment of BC.