NT5DC2 promotes leiomyosarcoma tumour cell growth via stabilizing unpalmitoylated TEAD4 and generating a positive feedback loop

• DOI: 10.1111/jcmm.16409
• Publication Date: 2021-05-16T07:53:28Z
• Authors: Bowen Hu; Shijie Zhou; Xuefeng Hu; Hua Zhang; Xiaorong Lan; Mei Li; Yunbing Wang; Qinsheng Hu
• Keywords: 0301 basic medicine; 03 medical and health sciences; Original Articles

Abstract 5′‐Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncoprotein, the regulatory effects of which have not been well characterized. This study aimed to investigate expression profile and functional regulation NT5DC2 its potential interplay with TEAD4 in leiomyosarcoma (LMS). Bioinformatic analysis was conducted using data from The Cancer Genome Atlas (TCGA) Genotype‐Tissue Expression (GTEx) program. LMS cell lines SK‐LMS‐1 SK‐UT‐1 were used for both vitro vivo analysis. Results showed that aberrantly upregulated LMS. Its overexpression associated unfavourable survival. Deletion significantly reduced cyclin B1, A2, E1 CDK1 increased G1 phase arrest lines, suppressed their proliferation vivo. interacted unpalmitoylated TEAD4, this association degradation via ubiquitin‐proteasome pathway. TRIM27 E3 ubiquitin ligase induces K27/48‐linked ubiquitination at Lys278. inhibition growth Dual‐luciferase assay demonstrated could bind promoter activate transcription. Based on these findings, we infer NT5DC2‐TEAD4 positive feedback loop plays an important role development might serve as therapeutic target.