MP17-10 N 6 -METHYLADENOSINE MODIFICATION OF CIRCANKS1A ACCELERATES CYTOPLASMIC EXPORT AND STABILIZES RACGAP1 TO PROMOTE BLADDER CANCER CELL PROLIFERATION AND METASTASIS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (MP17)1 Apr 2020MP17-10 N6-METHYLADENOSINE MODIFICATION OF CIRCANKS1A ACCELERATES CYTOPLASMIC EXPORT AND STABILIZES RACGAP1 TO PROMOTE BLADDER CANCER CELL PROLIFERATION AND METASTASIS Qiangqiang Ge*, Yang Xun, Junlin Lu, and Shaogang Wang Qiangqiang Ge*Qiangqiang Ge* More articles by this author , Yang XunYang Xun More articles by this author , Junlin LuJunlin Lu More articles by this author , and Shaogang WangShaogang Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000842.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Circular RNAs (circRNAs) have been identified to serve as significant regulators in cancer progression. However, the role of circRNA in bladder cancer (BCa) remains largely unknown. Herein, we investigate the expression profiles of circRNA in 20 paired samples of BCa. METHODS: To investigate the the expression profiles of circRNA, we performed high-throughput CircRNA Microarray using 20 pairs of BCa and matched adjacent non-tumor tissue samples. To explore crucial circRNAs that involved in BCa, co-expression network analysis was performed between the top 100 mostly changed circRNAs. The network represented that 15 circRNAs might involve in BCa progression. Analysis of the correlation between the expression level of 15 circRNAs and clinical data was conducted and circANKS1A was chosen. Gain-of-function and loss-of-function experiments were used to analyze the effect of circANKS1A on cell proliferation and metastasis in vitro and in vivo. m6A-containing RNAs were precipitated from methylated RNA immunoprecipitation (MeRIP) assays. The role of m6A methylation of circANKS1A in BCa proliferation and metastasis was investigated. To explore the potential molecular mechanisms of circANKS1A in regulating BCa malignance, RNA pull-down assays and mass spectrometry analysis were performed to screen circANKS1A-interacting proteins. RESULTS: By evaluating the co-expression network of differentially expressed circRNAs, we identify an N6-methyladenosine (m6A) modified circRNA, circANKS1A, upregulated in serum samples and tumor tissues from BCa patients with muscle invasive bladder Cancer (MIBC). What's more, circANKS1A upregulation is correlated with higher TNM stage and larger tumor size in BCa patients, and predicts poorer patient survival. Elevated circANKS1A promotes cell proliferation both in vitro and in vivo. The upregulated expression of circANKS1A facilitates cancer cells migration in vitro and promotes lung metastasis and liver metastasis in PDX metastasis models in vivo. Of note, N6-methyladenosine modification of circANKS1A accelerates export to the cytoplasm. By forming a circANKS1A/FOXM1/RACGAP1 RNA-protein ternary complex in the cytoplasm, circANKS1A enhances the stability of RACGAP1 mRNA to promote BCa cell proliferation and metastasis progression. Clinically, the upregulated expressions of circANKS1A and RACGAP1 are more prevalent in MIBC tissues than in non-muscle invasive bladder Cancer (NMIBC) tissues. CONCLUSIONS: N6-methyladenosine modification of circANKS1A modulates cytoplasmic export, stabilizes RACGAP1 to promote BCa cell proliferation and metastasis, and indicate that circANKS1A could serve as a significant prognostic marker and therapeutic target for BCa. Source of Funding: National Foundation Committee of Natural Sciences of China (grant numbers 81570631 and 81770704) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e229-e230 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiangqiang Ge* More articles by this author Yang Xun More articles by this author Junlin Lu More articles by this author Shaogang Wang More articles by this author Expand All Advertisement PDF downloadLoading ...