Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.643163
Keywords
long non-coding RNA; bladder cancer; TMPO-AS1; OTUB1
Categories
Funding
- National Natural Science Foundation of China [81874137]
- Outstanding Youth Foundation of Hunan Province [2018JJ1047]
- Huxiang Young Talent Project [2016RS3022]
- Hunan Province Science and Technology Talent Promotion Project [2019TJ-Q10]
- Independent Exploration and Innovation Project of Central South University [2019zzts825]
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The study reveals that TMPO-AS1 is upregulated in bladder cancer and promotes cell proliferation, migration, invasion, and inhibits apoptosis. Mechanistically, TMPO-AS1 interacts with E2F1, leading to E2F1 stabilization and ultimately promoting malignant behaviors in bladder cancer. Additionally, rescue experiments demonstrate that TMPO-AS1 promotes bladder cancer growth in an E2F1-dependent manner.
Background: Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis and progression. TMPO antisense RNA 1 (TMPO-AS1) has been found to be involved in several cancers by acting as a competing endogenous RNA. However, the potential roles of TMPO-AS1 in bladder cancer (BC) and the potential interactions with proteins remain poorly understood. Methods: The expression of the lncRNA TMPO-AS1 was evaluated via bioinformatic analysis and further validated by quantitative real-time PCR (qRT-PCR). Loss- and gain-of-function assays were performed to determine the biological functions of TMPO-AS1 in BC cell proliferation, migration, and invasion. Moreover, chromatin immunoprecipitation, Western blotting, and fluorescence in situ hybridization, as well as RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays, were conducted to explore the upstream and downstream molecules interacting with TMPO-AS1. Results: TMPO-AS1 is upregulated in BC. Functional experiments demonstrated that TMPO-AS1 promotes cell proliferation, migration, and invasion in BC and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization; therefore, TMPO-AS1 promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner. Conclusions: Our study is the first to uncover the novel TMPO-AS1/E2F1 positive regulatory loop important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.
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