Abstract 4721: Yin Yang 1-induced long non-coding RNA DUXAP9 drives oral squamous cell carcinoma by blocking CDK1-mediated EZH2 degradation

Abstract

Abstract Background: lncRNAs play a critical role in oral squamous cell carcinoma (OSCC) progression and metastasis. However, the detailed molecular mechanism is not fully understood. Methods: Differential-expressed lncRNAs between OSCCs and paired adjacent tissues were identified by microarray. The expression of lncRNADUXAP9 (DUXAP9) was detected by RNAscope and quantitative real-time PCR (qRT-PCR). The gain-of-function and loss-of-function of DUXAP9 were evaluated in vitro and in vivo assays. Chromatin immunoprecipitation (ChIP)and luciferase assays were performed to analyze the transcriptional regulation of DUXAP9. RNA pull-down assays, LS-MS/MS analysis, RNA immunoprecipitation assays, and Co-immunoprecipitation (Co-IP) were performed to address the molecular mechanism through which DUXAP9promotes OSCC progression. Results: By analyzing lncRNA microarray data, we identified a novel nuclear-localized DUXAP9, which is upregulated in OSCC. The high level of DUXAP9is positively associated with lymph-node metastasis, poor pathological differentiation, advanced clinical stage, worse overall survival, and worse disease-specific survival in OSCC patients. DUXAP9 significantly promotes cell proliferation, migration/invasion, and metastasis in vitro and in vivo through an EZH2-dependent manner. Yin Yang 1(YY1) was found to activate the transcriptional expression of DUXAP9 in OSCC. Furthermore, DUXAP9was proven to physically interact with EZH2 and inhibit EZH2 degradation via the suppression of the phosphorylation of EZH2, thereby blocking EZH2nucleus to cytoplasm translocation. Conclusions: Here we demonstrated a novel mechanism mediated by lncRNA DUXAP9 at the posttranslational level, which contributes to OSCC progression, thus providing a promising target for OSCC therapy. Keywords: LncRNA DUXAP9, YY1, EZH2, Ubiquitination, Oral squamous cell carcinoma Citation Format: Wei Cao, Wenkai Zhou. Yin Yang 1-induced long non-coding RNA DUXAP9 drives oral squamous cell carcinoma by blocking CDK1-mediated EZH2 degradation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4721.