长链非编码 RNA Kcnq1ot1 通过 microRNA-7a-5p/Rtn3 轴促进脂多糖诱导的急性肺损伤。
Long noncoding RNA Kcnq1ot1 prompts lipopolysaccharide-induced acute lung injury by microRNA-7a-5p/Rtn3 axis.
机构信息
Department of Geriatrics, Daqing Qilfield General Hospital, Daqing, 163000, Heilongjiang, China.
Department of Prosthodontics, Daqing Qilfield General Hospital, Zhongkang Street No. 9, Sartu District, Daqing, 163000, Heilongjiang, China.
出版信息
Eur J Med Res. 2022 Mar 22;27(1):46. doi: 10.1186/s40001-022-00653-8.
BACKGROUND
Long noncoding RNA (lncRNA)-regulated mechanism in acute lung injury (ALI) has attracted special interests in study researches. We planned to disclose whether KCNQ1 overlapping transcript 1 (Kcnq1ot1) is involved in ALI and its mechanism.
METHODS
The lipopolysaccharide (LPS)-induced ALI model was established in mice. Kcnq1ot1, microRNA (miR)-7a-5p and Reticulon 3 (Rtn3) levels were measured in lung tissues of mice. The vector that changed Kcnq1ot1, miR-7a-5p and Rtn3 expression was injected into LPS-treated mice, and pathological damage, fibrosis, apoptosis and inflammatory response were subsequently examined in lung tissues. The relation between Kcnq1ot1 and miR-7a-5p, and that between miR-7a-5p and Rtn3 were identified.
RESULTS
Kcnq1ot1 and Rtn3 expression increased while miR-7a-5p expression decreased in LPS-treated mice. Reduced Kcnq1ot1 or elevated miR-7a-5p alleviated pathological damage, fibrosis, apoptosis and inflammatory response in ALI mice, while overexpressed Rtn3 worsened ALI in mice. Downregulation of Rtn3 reversed the exacerbation of miR-7a-5p downregulation in ALI mice. Kcnq1ot1 competitively bound to miR-7a-5p and miR-7a-5p negatively mediated Rtn3 expression.
CONCLUSION
Our experiments evidence that silencing Kcnq1ot1 upregulates miR-7a-5p to suppress Rtn3 expression, thereby diminishing LPS-induced ALI.
背景
长链非编码 RNA（lncRNA）在急性肺损伤（ALI）中的调控机制已成为研究热点。本研究旨在探讨 KCNQ1 重叠转录本 1（Kcnq1ot1）是否参与 ALI 及其作用机制。
方法
采用脂多糖（LPS）诱导的小鼠 ALI 模型，检测小鼠肺组织中 Kcnq1ot1、微小 RNA（miR）-7a-5p 和网蛋白 3（Rtn3）的水平。将改变 Kcnq1ot1、miR-7a-5p 和 Rtn3 表达的载体注入 LPS 处理的小鼠，随后检测肺组织的病理损伤、纤维化、细胞凋亡和炎症反应。鉴定 Kcnq1ot1 与 miR-7a-5p、miR-7a-5p 与 Rtn3 之间的关系。
结果
与对照组相比，LPS 处理组小鼠肺组织中 Kcnq1ot1 和 Rtn3 表达上调，miR-7a-5p 表达下调。下调 Kcnq1ot1 或上调 miR-7a-5p 可减轻 LPS 诱导的 ALI 小鼠的病理损伤、纤维化、细胞凋亡和炎症反应，而过表达 Rtn3 则加重了 ALI 小鼠的损伤。下调 Rtn3 可逆转 miR-7a-5p 下调对 ALI 小鼠的加重作用。Kcnq1ot1 可与 miR-7a-5p 竞争性结合，miR-7a-5p 可负性调节 Rtn3 的表达。
结论
本研究证实沉默 Kcnq1ot1 可上调 miR-7a-5p 抑制 Rtn3 表达，从而减轻 LPS 诱导的 ALI。
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