LncRNA UCA1 Antagonizes Arsenic‐Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression

摘要: Arsenic (As) is a widespread metalloid contaminant, and its internal exposure demonstrated to cause serious detrimental health problems. Albeit considerable studies are performed interrogate the molecular mechanisms responsible for As-induced toxicities, exact not fully understood yet, especially at epigenetic regulation level. In present study, it identified that long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) alleviates G2/M phase arrest in human liver cells. Intensive mechanistic investigations illustrate UCA1 interacts with enhancer of zeste homolog 2 (EZH2) accelerates latter's protein turnover rate under normal As-exposure conditions. The phosphorylation EZH2 Thr-487 site by cyclin dependent kinase (CDK1) degradation, enhances this process through increasing interaction between CDK1 EZH2. As consequence, cell cycle regulator nuclear factor activated T cells (NFATc2), downstream target EZH2, upregulated resist As-blocked progress cytotoxicity. conclusion, findings decipher novel prosurvival signaling pathway underlying toxicity from perspective regulation: facilitates ubiquitination upregulate NFATc2 further antagonizes arrest.