In the present study, a novel signaling pathway of microRNA-141 (miR-141)/fused in sarcoma (FUS) was investigated in neuroblastoma (NB). Gene expression of miR-141 was evaluated in 6 NB cell lines. IMR-32 and SH-SY5Y cells were transduced with the miR-141 mimic lentivirus. The effects of miR-141 upregulation on cell proliferation, cell division, migration, chemosensitivity and in vivo explants were evaluated by MTT, cell cycle, wound-healing, cisplatin sensitivity and in vivo tumor growth assays, respectively. The correlation between miR-141 and the FUS gene was evaluated by luciferase assay and qRT-PCR. FUS was also downregulated in IMR-32 and SH-SY5Y cells to evaluate its impact on NB regulation. miR-141 was downregulated in both MYCN- and non-MYCN-amplified NB cell lines. In the IMR-32 and SH-SY5Y cells, lentivirus-induced miR-141 upregulation inhibited cancer proliferation, cell cycle progression, migration and increased cisplatin chemosensitivity in vitro. In addition, miR-141 upregulation reduced the in vivo growth of IMR-32 tumor explants. FUS was found to be inversely regulated by miR-141 in NB. Small interfering RNA (siRNA)-induced FUS downregulation had similar tumor-suppressive effects as miR-141 upregulation on NB cell proliferation, cell cycle progression, migration and cisplatin chemosensitivity. Our data indicate that miR-141 and the FUS gene, which are inversely correlated, play significant functional roles in regulating human NB.
In this study, we investigated the role of heme oxygenase-1 (HO-1) in intervertebral disc degeneration (IDD) by assessing the effects of HO-1 overexpression on IL-1β-induced apoptosis in nucleus pulposus cells (NPCs). Immunohistochemical staining showed HO-1 expression to be lower in NPCs from IDD patients than from patients with lumbar vertebral fractures (LVF). Western blot analysis showed HO-1 and LC3-II/I levels to be lower in NP tissues from IDD patients than from LVF patients, suggesting suppression of autophagy in degenerative intervertebral disc. Consistent with that idea, autophagy was increased in HO-1-overexpressing NPCs while IL-1β-induced apoptosis was reduced. These effects were reversed by treatment with the early autophagy inhibitor 3-methyl adenine, which suggests HO-1-induced autophagy suppresses IL-1β-induced apoptosis in NPCs. HO-1 overexpression promoted autophagy by increasing levels of Beclin-1/PI3KC3 complex. Phospho-P65 levels were lower in HO-1-overexpressing NPCs, suggesting inhibition of NF-κB-mediated apoptosis. Our study thus demonstrates that HO-1 promotes autophagy by enhancing formation of Beclin-1/PI3KC3 complex and suppresses IL-1β-induced apoptosis by inhibiting NF-κB. We suggest that HO-1 is a potential therapeutic target to alleviate IDD.
The adsorption of lysozyme is difficult to control by pH because of the relatively high isoelectric point of this protein (11.1). In this article, we demonstrate good control of lysozyme adsorption by pH in the range of 4-10 on silicon surfaces through modification with poly(2-(dimethylamino ethyl) methacrylate)-block-poly(methacrylic acid) (PDMAEMA-b-PMAA) diblock copolymer brushes. We show that the thickness of the outer PMAA block (lPMAA) is critical to the adsorption. When lPMAA was less than 10 nm, adsorption increased with increasing pH, and the difference in adsorption between high and low pH increased with lPMAA. The ratio of adsorption at pH 10 and pH 4 reached values as high as 16.4. When lPMAA was more than 10 nm, the adsorption tendency on the PDMAEMA-b-PMAA diblock copolymer brushes was similar to that on PMAA homopolymer brushes. These results indicate that the combination of PDMAEMA and PMAA gives adsorption behavior reflecting the properties of both polymers. However, if the outer PMAA block is thicker than a critical value, then the protein-resistant effect of the inner PDMAEMA block is screened.
The genetic variants play a crucial role in the pathogenesis of Alzheimer's disease (AD), while the relationships of specific single nucleotide polymorphisms (SNPs) with AD are still controversial. We performed the meta-analysis to obtain a more precise estimation of whether growth factor receptor-bound protein-associated binding protein 2 (GAB2), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1) variants are associated with AD. Databases including PubMed, Embase, and Cochrane Library were searched to find relevant studies. Cochran's Q-statistic and I were used to assess the heterogeneity among the included studies. Odds ratios (OR) and 95 % confidence intervals (95 % CIs) were conducted to evaluate the association between the SNP and the susceptibility to AD. Publication bias was estimated by funnel plots. All of the statistical analyses were implemented using R Version 3.2.1 software. A total of 35 case-control studies involving 15 SNPs were included. There was no significant association between SNPs of GAB2 rs2373115 (G> T) and PICALM rs541458 (C > T) and AD. The allele T of rs3851179 in PICALM was associated with a 13 % increase in the risk of AD. Seven SNPs on SORL1 were significantly associated with AD. Four SNPs, including rs1010159*T, rs641120*A, rs668387*T, and rs689021*A, were associated with a decreased risk of AD, while the other three SNPs, including rs12285364*T, rs2070045*G, and rs2282649*T, were all associated with an increased risk of AD. The results of the present study suggested that multiple gene variants were associated with AD. The SNP of rs3851179 (PICALM), rs12285364 (SORL1), rs2070045 (SORL1), and rs2282649 (SORL1) was associated with an increased risk of AD, whereas SORL1 rs1010159, rs641120, rs668387, and rs689021 were associated with a decreased risk of AD.
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