MALAT1 binds to miR-188-3p to regulate ALOX5 activity in the lung inflammatory response of neonatal bronchopulmonary dysplasia.
MALAT1 binds to miR-188-3p to regulate ALOX5 activity in the lung inflammatory response of neonatal bronchopulmonary dysplasia.
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DOI：
10.1016/j.molimm.2023.06.008
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发表时间：
2023-06
影响因子：
3.6
通讯作者：
D. Feng;Jia-He Chen;Yu-fei Chen;Q. Cao;Bingjie Li;Xiao‐qing Chen;R. Jin;Guo-Ping Zhou
中科院分区：
文献类型：
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作者：
D. Feng;Jia-He Chen;Yu-fei Chen;Q. Cao;Bingjie Li;Xiao‐qing Chen;R. Jin;Guo-Ping Zhou
支气管肺发育不良（BPD）是婴儿发病率和死亡率较高的疾病，但目前尚无有效的预防或治疗药物。在这项研究中，我们评估了MALAT1和ALOX5在BPD新生儿、高氧诱导大鼠模型和肺上皮细胞系外周血单核细胞中的表达。有趣的是，我们发现实验组MALAT1和ALOX5的表达上调，同时促炎细胞因子的表达上调。根据生物信息学预测，MALAT1和ALOX5同时结合miR-188-3p，在上述实验组中miR-188-3p下调。沉默MALAT1或ALOX5并过表达miR-188-3p可抑制高氧处理的A549细胞凋亡，促进细胞增殖。抑制MALAT1或过表达miR-188-3p会增加miR-188-3p的表达水平，但会降低ALOX5的表达水平。此外，RNA免疫沉淀（RIP）和荧光素酶检测显示，MALAT1直接靶向miR-188-3p调节BPD新生儿ALOX5的表达。总的来说，我们的研究表明MALAT1通过结合miR-188-3p调节ALOX5的表达，为BPD治疗的潜在治疗方法提供了新的见解。
Bronchopulmonary dysplasia (BPD) causes high morbidity and mortality in infants, but no effective preventive or therapeutic agents have been developed to combat BPD. In this study, we assessed the expression of MALAT1 and ALOX5 in peripheral blood mononuclear cells from BPD neonates, hyperoxia-induced rat models and lung epithelial cell lines. Interestingly, we found upregulated expression of MALAT1 and ALOX5 in the experimental groups, along with upregulated expression of proinflammatory cytokines. According to bioinformatics prediction, MALAT1 and ALOX5 simultaneously bind to miR-188–3p, which was downregulated in the experimental groups above. Silencing MALAT1 or ALOX5 and overexpressing miR-188–3p inhibited apoptosis and promoted the proliferation of hyperoxia-treated A549 cells. Suppressing MALAT1 or overexpressing miR-188–3p increased the expression levels of miR-188–3p but decreased the expression levels of ALOX5. Moreover, RNA immunoprecipitation (RIP) and luciferase assays showed that MALAT1 directly targeted miR-188–3p to regulate ALOX5 expression in BPD neonates. Collectively, our study demonstrates that MALAT1 regulates ALOX5 expression by binding to miR-188–3p, providing novel insights into potential therapeutics for BPD treatment.