MP01-06 EXOSOME-TRANSMITTED LONG NON-CODING RNA PLAT1 RECRUITS HNRNPA1 TO PROMOTE LYMPHATIC METASTASIS OF BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP01)1 Apr 2020MP01-06 EXOSOME-TRANSMITTED LONG NON-CODING RNA PLAT1 RECRUITS HNRNPA1 TO PROMOTE LYMPHATIC METASTASIS OF BLADDER CANCER Changhao Chen*, Tianxin Lin, and Jian Huang Changhao Chen*Changhao Chen* More articles by this author , Tianxin LinTianxin Lin More articles by this author , and Jian HuangJian Huang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000815.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer is one of the most common genitourinary malignancy and the eighth leading cause of cancer-related death among males. LN metastasis confers to a poor prognosis of bladder cancer patients. Recent studies show that exosomal long non-coding RNAs (lncRNAs) are essential to the metastasis of human cancers. However, the underlying mechanisms of exosomal lncRNAs in LN metastasis of bladder cancer have not yet been elucidated. METHODS: RNA-sequencing identified the differentially expressed lncRNAs in urinary exosomes from bladder cancer patients and healthy controls. In vitro and in vivo experiments were used to evaluate the functional role of exosomal PLAT1. Pull-down and RIP assays were used to confirm the binding partner of PLAT1. ChIRP assays were utilized to examine the interaction of PLAT1 and IκBα promoter. ChIP assays assessed the H3K27e3 level in IκBα promoter. RESULTS: PLAT1 was identified as a exosomal lncRNA which was overexpressed in bladder cancer-secreted exosomes and correlated with the LN metastasis of bladder cancer. Overexpression of exosomal PLAT1 induced the lymphangiogenesis of bladder cancer in vitro. Consistently, exosomal PLAT1 overexpression facilitated LN metastasis of bladder cancer in popliteal LN metastasis model. Moreover, PLAT1 interacted with hnRNPA1, which further sorted PLAT1 into exosomes. PLAT1 encapsulated with exosomes was transmitted into human lymphatic endothelial cells (HLECs) and downregulated IκBα expression by recruiting hnRNPA1 to the promoter region of PROX1 and increasing H3K27me3 level. Furthermore, IκBα downregulation-mediated NF-κB signaling activation activated the expression of PROX1 and VEGF-C, which led to the lymphangiogenesis and LN metastasis of bladder cancer. CONCLUSIONS: Identification of exosomal PLAT1 for inducing lymphangiogenesis and lymphatic metastasis not only increases our knowledge of the biological basis for LN metastasis regulation but also develops a potential therapeutic target for LN metastasis in bladder cancer. Source of Funding: This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81802530, 81672395, 81702951, 81672395, 81672807, 81702417, 81000917, 81402213, and 81370059), the Guangdong Science and Technology Department (Grant No. 2018A030313564, S2012010008934, 2014A030313044, 2014A030311047, 2016A030313340, 2016A030313296, and 2017A030313880). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e3-e4 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Changhao Chen* More articles by this author Tianxin Lin More articles by this author Jian Huang More articles by this author Expand All Advertisement PDF downloadLoading ...