PD53-03 SCHISTOSOMA HAEMATOBIUM MAY PROMOTE BLADDER CARCINOGENESIS THROUGH DNA BINDING OF ITS HOMOLOG OF THE INTERLEUKIN-4-INDUCING PRINCIPLE FROM SCHISTOSOMA MANSONI EGGS

Abstract

You have accessJournal of UrologyCME1 May 2022PD53-03 SCHISTOSOMA HAEMATOBIUM MAY PROMOTE BLADDER CARCINOGENESIS THROUGH DNA BINDING OF ITS HOMOLOG OF THE INTERLEUKIN-4-INDUCING PRINCIPLE FROM SCHISTOSOMA MANSONI EGGS Derick Osakunor, Trevor Siggers, Olivia Lamanna, Kenji Ishida, Heather Hook, and Michael Hsieh Derick OsakunorDerick Osakunor More articles by this author , Trevor SiggersTrevor Siggers More articles by this author , Olivia LamannaOlivia Lamanna More articles by this author , Kenji IshidaKenji Ishida More articles by this author , Heather HookHeather Hook More articles by this author , and Michael HsiehMichael Hsieh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002630.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urogenital schistosomiasis, caused by Schistosoma haematobium, is the most common form of schistosomiasis worldwide and is well-known for its association with bladder cancer. However, the underlying mechanisms for the causal link between S. haematobium and bladder cancer, are poorly understood. Interleukin-4-inducing principle from Schistosoma mansoni eggs (IPSE) is the most abundant secreted protein from eggs of all schistosome species and plays a major role in modulating host pathology. We have previously demonstrated that H-IPSE, the S. haematobium homolog of IPSE, is internalized by both endothelial and urothelial cells, drives endothelial and urothelial proliferation, and may thus be involved in S. haematobium-related carcinogenesis. METHODS: Here, we used protein binding microarray (PBM) technology and bioinformatics approaches to determine the specific DNA binding motifs of H-IPSE, and the downstream transcriptional events that result from DNA binding. RESULTS: Our results showed that DNA binding of H-IPSE is highly specific, and a DNA-binding motif of GGGTGGG was determined. The GGGTGGG sequence is recognized by the transcription factors PuF and Sall2, which are involved in tumor suppression by binding to the promoter of c-myc. Concurrent experiments with M-IPSE (the S. mansoni homolog) showed that M-IPSE has the DNA binding motif resembling GGGGGAAAA and is different from H-IPSE, although similar in their affinity for G-rich sequences. CONCLUSIONS: Together, our results enabled us to identify novel molecular targets of H-IPSE that may explain its role in carcinogenesis. The differences in DNA binding motifs for H-IPSE and M-IPSE may likely explain why S. haematobium, but not S. mansoni, is carcinogenic. Source of Funding: NIH R01DK113504 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e910 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Derick Osakunor More articles by this author Trevor Siggers More articles by this author Olivia Lamanna More articles by this author Kenji Ishida More articles by this author Heather Hook More articles by this author Michael Hsieh More articles by this author Expand All Advertisement PDF DownloadLoading ...