NF-κB 1-induced LINC00665 regulates inflammation and apoptosis of neurons caused by spinal cord injury by targeting miR-34a-5p
NF-κB 1-induced LINC00665 regulates inflammation and apoptosis of neurons caused by spinal cord injury by targeting miR-34a-5p
复制标题
NF-κB 1 诱导的 LINC00665 通过靶向 miR-34a-5p 调节脊髓损伤引起的神经元炎症和细胞凋亡。
DOI：
10.1080/01616412.2020.1866373
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发表时间：
2021-01-15
影响因子：
1.9
通讯作者：
Ma, Lizhong
中科院分区：
文献类型：
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作者：
Deng, Qilong;Ma, Lili;Ma, Lizhong
背景资料：脊髓损伤（Spinal cord injury，SCI）致残率高，治愈率低，给患者带来挫折感，给家庭带来沉重负担。本研究旨在探讨NF-κ B1是否能诱导LINC 00665的表达，并与miR-34 a-5 p形成反馈环，调节神经元的炎症和凋亡。结果：SCI大鼠Basso、Beattie和Bresnahan（BBB）评分降低，脊髓组织损伤加重，神经元数量减少。脊髓损伤大鼠血清中TNF-α、IL-1 β、IL-6水平及脊髓组织中LINC 00665、NF-κ B1表达均升高。经LPS诱导后，PC 12细胞活力下降。LPS诱导的PC 12细胞LINC 00665和NF-κ B1的表达增加，而NF-κ B抑制剂BAY 11 -7082可部分逆转这一变化。抑制LINC 00665可以提高细胞活力，抑制细胞凋亡和炎症，并下调脂多糖诱导的PC 12细胞中NF-κ B1的表达。此外，miR-34 a-5 p在LPS诱导的PC 12细胞中的表达降低，这可以通过抑制LINC 00665来促进。结论：抑制LINC 00665可提高LPS诱导的PC 12细胞的存活率，抑制细胞凋亡和炎症反应，NF-κ B1/LINC 00665/miR-34 a-5 ploop可能成为SCI治疗的有效靶点。
Background: Spinal cord injury (SCI) has high disability rate and low cure rate, which frustrates the patients and brings a heavy burden to their families. This study aimed to explore whether NF-kappa B1 could induce the expression of LINC00665 and form a feedback loop with miR-34a-5p to regulate inflammation and apoptosis of neurons.Results: Basso, Beattie, and Bresnahan (BBB) scoring was decreased, damage for spinal cord tissue was aggravated and neuron number was decreased in SCI rats. The levels of TNF-alpha, IL-1 beta and IL-6 in serum and the expression of LINC00665 and NF-kappa B1 in spinal cord tissues were all increased in SCI rats. After LPS induction, PC12 cell viability was decreased. The expression of LINC00665 and NF-kappa B1 in LPS-induced PC12 cells was increased, which was partially reversed by BAY11-7082 (NF-kappa B inhibitor). Inhibition of LINC00665 improved cell viability, suppressed apoptosis and inflammation and down-regulated the NF-kappa B1 expression in LPS-induced PC12 cells. Furthermore, miR-34a-5p expression was decreased in LPS-induced PC12 cells, which could be promoted by inhibition of LINC00665. miR-34a-5p inhibitor restrained the effect of inhibition of LINC00665 on NF-kappa B1 expression in LPS-induced PC12 cells.Conclusion: inhibition of LINC00665 improved cell viability, suppressed apoptosis and inflammation in LPS-induced PC12 cells, and the NF-kappa B1/LINC00665/miR-34a-5ploop might be a useful therapeutic target in SCI treatment.