Mitosis targeting in non-small lung cancer cells by inhibition of PAD4
Xiangmei Wu,
Liujia Chan,
Di Zhu,
Yuheng Pang,
Mulan Jin,
Yuji Wang,
Wenjing Wang
Affiliations
Xiangmei Wu
Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 150086, China; Department of Pathology, Beijing Geriatric Hospital, Beijing, 100095, China
Liujia Chan
Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China; Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, China
Di Zhu
Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, China
Yuheng Pang
Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
Mulan Jin
Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 150086, China; Corresponding author.
Yuji Wang
Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, China; Corresponding author.
Wenjing Wang
Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China; Corresponding author.
PAD4 expression and activity were significantly up-regulated in lung cancer tissues suggesting that PAD4 could be a possible target for lung cancer treatment. In this study we had demonstrated that PAD4 expression was higher in lung cancer patients whom with lymphnode metastasis and pleural invasion. Inhibiting PAD4 with a small molecular inhibitor could induce apoptosis and suppress growth in lung cancer cells. We used RNA-sequencing to further investigate transcriptional changes that induced by PAD4 inhibition, and results suggested its affected mostly on the cell cycle, mitotic cell cycle process, p53 signaling pathway. By using image flow cytometry analysis, we found that PAD4 inhibited by YW3-56 could accumulate cells in the G1/G0 phases and reducing the fraction of G2/M and S phase cells. Quantification of different phase of mitosis in cells treated with YW3-56 revealed an increasing trend of telophase and prophase cells. Taken together, our data indicated that PAD4 inhibitor could affect cell cycle and mitosis of lung cancer cells, and targeting PAD4 could be a promising strategy for discovery novel anti-NSCLC treatments.
