Knockdown of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) enhances tumorigenesis both in vivo and in vitro in bladder cancer

Bladder cancer is the most common tumor of the urinary tract. Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), a gene encoding the 14-3-3ζ protein, has been observed to be frequently amplified in bladder cancer. However, the role of 14-3-3ζ in various types of cancer is controversial. With reproduction of The Cancer Genome Atlas database, we searched the correlation of YWHAZ expression with survival outcomes of multiple cancers in silico. Our results revealed that only in bladder cancer was there a positive survival trend with YWHAZ overexpression. To study its role in bladder cancer, YWHAZ was successfully downregulated by lentivirus in 5637 and T24 cells. MTT and colony-formation assays showed that YWHAZ downregulation increased cell proliferation. Wound healing and Transwell assays showed that YWHAZ downregulation enhanced cell migration and invasiveness. FACS analysis showed that YWHAZ induced cell cycle arrest, but not apoptosis. A xenograft tumor model revealed that YWHAZ knockdown enhanced tumor growth. Gene set enrichment analysis confirmed that the cell cycle pathway plays a vital role in the function of the YWHAZ gene. In conclusion, knockdown of YWHAZ promoted both in vitro and in vivo tumorigenesis in bladder cancer and may be a novel biomarker for bladder cancer deserving further study.