LncRNA MALAT1 facilitates Parkinson's disease progression by increasing SOCS3 promoter methylation.

BACKGROUND: Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to be involved in Parkinson's disease (PD) progression, but its mechanism needs to be further explored. METHODS: Mice were injected with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD mice models, and BV2 cells were treated with lipopolysaccharides (LPS) to mimic PD cell models. MALAT1 expression and suppressor of cytokine signaling 3 (SOCS3) protein level were examined using quantitative real-time PCR and western blot, respectively. Cell functions were tested by cell counting kit 8 assay and flow cytometry. The interaction between MALAT1 and SOCS3 was confirmed using RNA pull-down and RIP assays. RESULTS: MALAT1 was upregulated in MPTP-induced PD mice and LPS-induced BV2 cells. Silencing of MALAT1 increased viability, while inhibited apoptosis and inflammation in LPS-induced BV2 cells. Besides, MALAT1 enhanced the SOCS3 promoter methylation to decrease its expression by recruiting DNMT1, DNMT3A and DNMT3B. Furthermore, SOCS3 knockdown eliminated sh-MALAT1-mediated the inhibition effect on LPS-induced BV2 cell injury. In vivo, MALAT1 silencing ameliorated neurological impairment and neuroinflammation in MPTP-induced PD mice. CONCLUSION: Our data revealed that MALAT1 worsened PD processes via inhibiting SOCS3 expression by increasing its promoter methylation.

LncRNA SOX21-AS1 Promotes Activation of BV2 Cells via Epigenetical Silencing of SOCS3 and Aggravates Parkinson's Disease.

BACKGROUND: LncRNAs perform a crucial impact on microglia's activation in Parkinson's disease (PD). Here, our purpose was to probe the function and involved mechanism of lncRNA SOX21-AS1 on microglial activation in PD. METHODS: Mice were treated with MPTP, and BV2 cells were treated with LPS/ATP to build PD animal and cell models. Genes' expression was measured using RT-qPCR, immunoblotting, and IHC stain. ELISA was applied for testing inflammatory factors' levels. Cell viability and apoptosis were tested using kits. RIP and RNA pull-down assay were utilized for monitoring the bond of SOX21-AS1 to EZH2, and ChIP was applied for affirming the bond between EZH2 and SOCS3's promoter. RESULTS: The expression of SOX21-AS1 and SOCS3 was abnormal in PD cell and animal models. Inhibition of SOX21-AS1 repressed LPS/ATP-induced activation in BV2 cells and nerve damage caused by activated BV2 cells, alleviating the pathological features of PD mice. Further studies found that SOX21-AS1 epigenetically inhibited SOCS3 by recruiting EZH2 to SOCS3 promoter. SOX21-AS1 overexpression partially offset the repressive impact of SOCS3 enhancement on BV2 cell activation and the protective effect on nerve cells. CONCLUSION: SOX21-AS1 enhances LPS/ATP-induced activation of BV2 cells and nerve damage caused by activated BV2 cells though recruiting EZH2 to SOCS3's promoter, thereby alleviating PD progression. Our research supplies new potential target for curing PD.