长链非编码 RNA SNHG6 通过调节 miR-335 激活 KLF5/NF-κB 通路促进高氧诱导的肺细胞损伤。
LncRNA SNHG6 accelerates hyperoxia-induced lung cell injury via regulating miR-335 to activate KLF5/NF-κB pathway.
机构信息
Department of Respiratory, Hunan Children's Hospital, Changsha 410007, Hunan Province, China.
Department of Respiratory, Hunan Children's Hospital, Changsha 410007, Hunan Province, China.
出版信息
Cytokine. 2022 Sep;157:155914. doi: 10.1016/j.cyto.2022.155914. Epub 2022 Jul 6.
BACKGROUND
Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, and its pathogenesis has not been clarified. Long non-coding RNAs (lncRNA) have important functions in cell bioactivity. However, their role in developmental lung disease remains unclear.
OBJECTIVE
The aim of this study was to demonstrate the role of lncRNA SNHG6 (SNHG6) in BPD and its underlying mechanisms.
METHODS
The blood of patients with BPD were collected, and BPD model of BEAS-2B cells was established by hyperoxia method. SNHG6, miR-335 and KLF5 mRNA expression were detected by RT-qPCR. Western blot was conducted to measure the levels of apoptosis-related proteins' expression and NF-κB pathway related proteins. BEAS-2B cell viability and apoptosis were assessed by CCK-8 and flow cytometry, respectively. Assay Kit was applied to detect ROS, MDA and SOD levels, respectively. ELISA was performed to assess the levels of inflammatory factors. The binding site of miR-335 with SNHG6 or KLF5 were predicted by using DIANA or TargetScan, and which was verified by double luciferase reporter assay.
RESULTS
Firstly, SNHG6 was highly expressed and miR-335 was lowly expressed in BPD model, SNHG6 knockdown and miR-335 mimics both alleviated hyperoxia-induced lung cell injury, and SNHG6 targeted miR-335. Subsequently, KLF5 was targeted by miR-335, and KLF5 promoted lung cell injury via activating NF-κB pathway. Furthermore, SNHG6 mediated lung cell injury via regulating the miR-335/KLF5/NF-κB pathway.
CONCLUSION
Our research confirmed that SNHG6 mediated hyperoxia-induced lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. These findings suggest that SNHG6 serves as promising targets for the treatment of newborns with BPD.
背景
支气管肺发育不良（BPD）是早产儿常见的慢性肺部疾病，其发病机制尚未阐明。长链非编码 RNA（lncRNA）在细胞生物活性中具有重要作用。然而，它们在发育性肺部疾病中的作用尚不清楚。
目的
本研究旨在探讨 lncRNA SNHG6（SNHG6）在 BPD 中的作用及其潜在机制。
方法
收集 BPD 患者的血液，采用高氧法建立 BEAS-2B 细胞 BPD 模型。采用 RT-qPCR 检测 SNHG6、miR-335 和 KLF5 mRNA 表达。采用 Western blot 检测凋亡相关蛋白表达和 NF-κB 通路相关蛋白水平。采用 CCK-8 法和流式细胞术分别检测 BEAS-2B 细胞活力和凋亡。采用试剂盒分别检测 ROS、MDA 和 SOD 水平。采用 ELISA 法检测炎症因子水平。采用 DIANA 或 TargetScan 预测 miR-335 与 SNHG6 或 KLF5 的结合位点，并通过双荧光素酶报告基因实验验证。
结果
首先，在 BPD 模型中 SNHG6 高表达，miR-335 低表达，SNHG6 敲低和 miR-335 模拟物均可减轻高氧诱导的肺细胞损伤，且 SNHG6 靶向 miR-335。随后，miR-335 靶向 KLF5，通过激活 NF-κB 通路促进肺细胞损伤。此外，SNHG6 通过调节 miR-335/KLF5/NF-κB 通路介导肺细胞损伤。
结论
本研究证实 SNHG6 通过调节 miR-335/KLF5/NF-κB 通路介导高氧诱导的肺细胞损伤。这些发现表明 SNHG6 可能成为治疗新生儿 BPD 的有前途的靶点。
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