LncRNA UCA1 attenuates autophagy-dependent cell death through blocking autophagic flux under arsenic stress
Gao, M; Li, C; Xu, M; Liu, Y; Liu, S
| HERO ID | 4242038 |
|---|---|
| In Press | No |
| Year | 2018 |
| Title | LncRNA UCA1 attenuates autophagy-dependent cell death through blocking autophagic flux under arsenic stress |
| Authors | Gao, M; Li, C; Xu, M; Liu, Y; Liu, S |
| Journal | Toxicology Letters |
| Volume | 284 |
| Page Numbers | 195-204 |
| Abstract | Arsenic (As) is a naturally toxin which exists ubiquitously in foods and various environment media, incurring diverse toxicities and health problems. Previous studies have shown that oxidative stress, genotoxic damage and pro-apoptotic pathways are ascribed to As-associated detrimental effects. Meanwhile, epigenetic regulations (such as miRNAs and histone modifications) were also reported to contribute to As-induced adverse effects. Nonetheless, whether long non-coding RNAs (LncRNAs) are indispensable for the regulation of As-induced biological outcomes are nearly unknown. In this study, we identified that a lncRNA UCA1 was markedly induced by As treatment in human hepatocytes. Functional assessments revealed that UCA1 played a critical role in protecting hepatocytes from As-induced autophagy inhibition. Furthermore, through RNA-seq assay, oxidative stress induced growth inhibitor 1 (OSGIN1) was uncovered to be the most responsive target downstream of UCA1, and miR-184 acted as an intermediate for the regulation of UCA1 on the level of OSGIN1 through a competing endogenous RNAs (ceRNAs) mechanism. Further mechanistic investigations demonstrated that UCA1/OSGIN1 signaling contributed to As-induced autophagic flux blockage through activating mTOR/p70S6 K cascade, resulting in compromised cell death. Collectively, our study deciphered a lncRNA-dictated molecular mechanism responsible for As toxicity: UCA1 leads a protective role against As-induced cell death through blocking autophagic flux. |
| Doi | 10.1016/j.toxlet.2017.12.009 |
| Pmid | 29248574 |
| Wosid | WOS:000425265800023 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |