MiR-654-3p, reduced by the excessive ALKBH5, Alleviated the Inflammation in OA by targeting TNFRSF9, the trigger of the NF-κB pathway.
MiR-654-3p, reduced by the excessive ALKBH5, Alleviated the Inflammation in OA by targeting TNFRSF9, the trigger of the NF-κB pathway.
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DOI：
10.1016/j.bbrc.2022.09.103
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发表时间：
2022-10
影响因子：
3.1
通讯作者：
Baoxi Yu;Anyu Zeng;Hailong Liu;Zhijian Yang;Ming Fu
中科院分区：
文献类型：
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作者：
Baoxi Yu;Anyu Zeng;Hailong Liu;Zhijian Yang;Ming Fu
MicroRNA （miRNA）是骨关节炎（OA）最有效的治疗靶点之一。我们发现miR-654-3p保护软骨细胞的表型。基于双荧光素酶报告基因实验和RNA结合蛋白免疫沉淀（RIP）实验，我们证明TNF受体超家族成员9 （TNFRSF9）通过结合miR-654-3p的3'UTR区域成为miR-654-3p的靶标。此外，进一步的实验证实TNFRSF9作为NF-κB通路的触发因子与软骨细胞炎症相关。在小鼠膝关节中过表达MiR-654-3p可减轻体内OA。此外，我们检测了OA中的m6A酶水平，证明α-酮戊二酸依赖性双加氧酶alkB同源物5 （ALKBH5）的异常表达导致了miR-654-3p的降低。我们的研究说明了miR-654-3p在OA中的重要作用，包括其成熟和保护软骨细胞表型的机制，它可能是OA的一个新的治疗靶点。
MicroRNA (miRNA) is one of the most potent therapeutic targets for osteoarthritis (OA). We identified that miR-654-3p protected the phenotype of chondrocytes. We demonstrated that TNF receptor superfamily member 9 (TNFRSF9) was the target of miR-654-3p by binding to its 3′UTR regions, based on a dual-luciferase reporter assay and an RNA binding protein immunoprecipitation (RIP) assay. In addition, further experiments proved that TNFRSF9, as a trigger of the NF-κB pathway, correlated with the inflammation in chondrocytes. MiR-654-3p overexpressed in the knee of mice alleviated the OA in vivo. Moreover, we examined the m6A enzyme level in OA, proving that the abnormal expression of α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) contributed to the miR-654-3p decrease. Our research illustrated the significant role of miR-654-3p in OA, including its maturation and the mechanism in protecting the phenotype of chondrocytes, which could be a new treatment target for OA.