Peptidyl Arginine Deiminase, Type II (PADI2) Is Involved in Urothelial Bladder Cancer.

Peptidyl arginine deiminase, type II expression has been shown to potentiate multiple different carcinogenesis pathway including breast carcinoma and spontaneous skin neoplasia. The objective of this study was to examine the role of in urothelial bladder cancer which has not been evaluated previously. Analysis of mutation and genome amplification of bladder cancer within The Cancer Genome Atlas (TCGA) showed that duanyu1563I2 is both mutated and amplified in a cohort of bladder cancer patients, with the largest number of mutations detected in urothelial bladder cancer. Even though duanyu1563I2 expression was not significantly correlated to survival in bladder cancer patients, it was significantly overexpressed at the mRNA and protein levels, as revealed by TCGA data and immunohistochemistry analysis, respectively. duanyu1563I2 showed wide expression pattern in bladder cancer tissues but was hardly detected in tumor adjacent normal tissue. mediated silencing of duanyu1563I2 in the bladder cancer cell line T24 did not result in a change of proliferation. Interestingly knockdown of duanyu1563I2 expression did not affect Snail1 protein, which is associated with metastatic progression, in these cells. However, duanyu1563I2 silencing remarkably attenuated both in vitro migration and invasion- in T24 cells indicating a Snail1-independent effect of duanyu1563I2 on invasive potential of urothelial bladder cancer. This was further corroborated by in vivo xenograft assays where duanyu1563I2 shRNA harboring T24 cells did not have detectable tumors by week 4 as compared to robust tumors in the control Luciferase shRNA harboring cells. duanyu1563I2 silencing did not affect proliferation rates and hence this would suggest that duanyu1563I2 knockdown is perhaps causing increased apoptosis as well as transition through the cell cycle, which needs to be confirmed in future studies. Our results reveal a yet undefined role of duanyu1563I2 as an oncogene in urothelial bladder cancer.

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