Abstract 4822: The 3'UTR of CAPZA1 functions separately and oppositely to its host gene in ESCC

Abstract

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and highly prevalent in China. According to our previous study on whole-genome sequencing (WGS) and whole-exome sequencing (WES) of ESCC, we identified that CAPZA1 displayed copy number losses in the ESCC sequencing cohort. CAPZA1, which modulates the dynamic assembly of actin filament and cell motility, has been reported dysregulated expression in neuroblastoma, gastric cancer, liver cancer and breast cancer. However, the functional role and the underlying mechanism of CAPZA1 in ESCC have not been elucidated. Here, we identify the expression of CAPZA1 significantly decreased in cancer tissues than in normal tissues by immunohistochemical assay. Through gain and loss of function approaches, we found that CAPZA1 suppressed the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Moreover, we found that CAPZA1 promoted the expression of E-cadherin, while decreased the expression of Vimentin and Twist. Intriguingly, we demonstrated that the 3'UTR of CAPZA1 could function as an independent RNA molecule separately with a full length of 1487nt by RACE and Northern-blot assays. Furthermore, the RNA in situ hybridization assay was employed to validate that 3'UTR expression levels were significantly higher in cancer tissues than in normal tissues. Additionally, the 3'UTR promoted cell migratory and invasive capabilities, which is oppositely to its host gene CAPZA1. The 3'UTR performed oncogenic role by enhancing the combination of IGF2BPs proteins to c-myc mRNA and promoted the translation of c-myc. These findings offer a new dimension to the crosstalk between 3'UTR and its host gene, which may open new ways towards additional therapeutic strategies in the treatment of ESCC. Citation Format: Dan Li, Nan Kang, Zhangfu Li, Qimin Zhan. The 3'UTR of CAPZA1 functions separately and oppositely to its host gene in ESCC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4822.