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| LncRNA MALAT1 Mediates Epigenetic Silencing of Systemic Lupus Erythematosus-Associated Anti-Inflammatory Genes through Recruitment of EZH2 |
| GAO Fei, TAN Yuan, ZHANG Lian, et al |
| Changsha First Hospital, Hunan Changsha 410005, China |
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Abstract Objective: To explore the correlation of long non-coding RNA (LncRNA) MALAT1 and methyltransferase EZH2 with SLE-associated anti-inflammatory factors and the molecular regulatory mechanism.Methods: Peripheral blood mononuclear cells (PBMC) were extracted from healthy controls (n=10) and SLE patients (n=10), and mRNA levels of LncRNA MALAT1, EZH2, and anti-inflammatory factors PTEN, Ets-1, and FOXO1 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The correlation between LncRNA MALAT1, EZH2, and the expression of stress factors was verified respectively. After transfecting THP-1 cells with small interfering RNA (si-RNA), the expression of various anti-inflammatory factors was detected by RT-qPCR after LncRNA MALAT1 and EZH2 was knocked down, and the interaction between LncRNAMALAT1 and EZH2 was verified by RNA immunoprecipitation (RIP). After simultaneous knockdown of EZH2 and overexpression of LncRNAMALAT1, the 27th lysine (K27) trimethylation (me3) level of histone 3 (H3) was detected by Western blot (western blot).Results: Compared with healthy controls, PBMC LncRNAMALAT1 and EZH2 in peripheral blood of SLE patients were significantly overexpressed (P<0.05), anti-inflammatory factors PTEN, Ets-1, and FOXO1 were significantly decreased (P<0.05), and LncRNA MALAT1 and EZH2 were significantly negatively correlated with the anti-inflammatory expressions. The expressions of various anti-inflammatory factors were significantly increased after LncRNA MALAT1 and EZH2 were knocked down respectively (P<0.05). The RIP result shows that LncRNA MALAT1 and EZH2 combine. After overexpression of LncRNA MALAT1, the expression of anti-inflammatory factors was significantly decreased. Still, the expression of anti-inflammatory factors was increased and H3K27me3 was decreased considerably when EZH2 was knocked down and LncRNA MALAT1 was overexpressed at the same time (P<0.05).Conclusion: The expression of LncRNA MALAT1 and EZH2 is significantly negatively correlated with the expression of SLE- associated anti-inflammatory factors, and the molecular mechanism is related to LncRNA MALAT1 regulating the expression of H3K27me3 by recruiting EZH2.
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. [J]. HeBei Med, 2024, 30(8): 1406-1408. |
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2024, Vol. 30 
