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

Abstract

Peptidyl arginine deiminase, type II (PADI2) 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 PADI2 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 PADI2 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 PADI2 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. PADI2 showed wide expression pattern in bladder cancer tissues but was hardly detected in tumor adjacent normal tissue. RNAi mediated silencing of PADI2 in the bladder cancer cell line T24 did not result in a change of proliferation. Interestingly knockdown of PADI2 expression did not affect Snail1 protein, which is associated with metastatic progression, in these cells. However, PADI2 silencing remarkably attenuated both in vitro migration and invasion- in T24 cells indicating a Snail1-independent effect of PADI2 on invasive potential of urothelial bladder cancer. This was further corroborated by in vivo xenograft assays where PADI2 shRNA harboring T24 cells did not have detectable tumors by week 4 as compared to robust tumors in the control Luciferase shRNA harboring cells. PADI2 silencing did not affect proliferation rates and hence this would suggest that PADI2 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 PADI2 as an oncogene in urothelial bladder cancer.

• Authors: Bao-Shan Gao, Chun-Shu Rong, Hong-Mei Xu, Tao Sun, Jie Hou, Ying Xu
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 26 Issue 2 Pg. 1279-1285 (Apr 2020) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 31267364 (Publication Type: Journal Article)

Chemical References

• PADI2 protein, human
• Protein-Arginine Deiminase Type 2

Topics

• Animals
• Carcinogenesis (genetics)
• Carcinoma, Transitional Cell (genetics, pathology)
• Female
• Heterografts
• Humans
• Male
• Mice
• Mice, Nude
• Protein-Arginine Deiminase Type 2 (genetics, metabolism)
• Urinary Bladder Neoplasms (genetics, pathology)