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Hsa_circ_0005567 Activates Autophagy and Suppresses IL-1β-Induced Chondrocyte Apoptosis by Regulating miR-495
Frontiers in Molecular Biosciences ( IF 5 ) Pub Date : 2020-08-04 , DOI: 10.3389/fmolb.2020.00216
Jinling Zhang , Fangyue Cheng , Genxiang Rong , Zhi Tang , Binjie Gui

Excessive chondrocyte apoptosis is mostly responsible for the progression of osteoarthritis (OA). It has been shown that circular RNAs (circRNAs) are differentially expressed in OA cartilage and participate in various pathological processes during OA. Here, this study was designed to explore the effect and molecular mechanism of hsa_circ_0005567 on IL-1β-induced chondrocyte apoptosis. The results showed that hsa_circ_0005567 knockdown aggravated the IL-1β-induced chondrocyte apoptosis. In contrast, hsa_circ_0005567 overexpression attenuated the IL-1β-induced chondrocyte apoptosis, but this effect could be abrogated by 3-methyladenine (an inhibitor of autophagy), suggesting that hsa_circ_0005567 overexpression inhibited chondrocyte apoptosis by inducing autophagy. Furthermore, hsa_circ_0005567 competitively bound to miR-495 and derepressed the expression of ATG14, an early autophagy marker that was a direct target of miR-495. Moreover, both miR-495 mimic and ATG14 knockdown counteracted the autophagy-promoting and anti-apoptotic effects of hsa_circ_0005567 overexpression in IL-1β-treated chondrocytes. Taken together, hsa_circ_0005567 activates autophagy by regulating the miR-495/ATG14 axis and thereby suppresses IL-1β-induced chondrocyte apoptosis. These findings suggest that hsa_circ_0005567 may serve as a therapeutic target for the treatment of OA.



中文翻译:

Hsa_circ_0005567通过调节miR-495激活自噬并抑制IL-1β诱导的软骨细胞凋亡

过度的软骨细胞凋亡是导致骨关节炎(OA)发展的主要原因。已经显示,环形RNA(circRNA)在OA软骨中差异表达,并参与OA期间的各种病理过程。在这里,本研究旨在探讨hsa_circ_0005567对IL-1β诱导的软骨细胞凋亡的影响及其分子机制。结果表明,hsa_circ_0005567敲低加重了IL-1β诱导的软骨细胞凋亡。相反,hsa_circ_0005567的过表达减弱了IL-1β诱导的软骨细胞凋亡,但这种作用可能被3-甲基腺嘌呤(自噬抑制剂)所废止,表明hsa_circ_0005567的过表达通过诱导自噬抑制了软骨细胞的凋亡。此外,hsa_circ_0005567与miR-495竞争性结合并抑制ATG14的表达,ATG14是早期自噬标记,是miR-495的直接靶标。此外,miR-495模拟物和ATG14组合物均抵消了IL-1β处理的软骨细胞中hsa_circ_0005567过表达的自噬促进和抗凋亡作用。总之,hsa_circ_0005567通过调节miR-495 / ATG14轴来激活自噬,从而抑制IL-1β诱导的软骨细胞凋亡。这些发现表明hsa_circ_0005567可以用作OA的治疗靶标。hsa_circ_0005567通过调节miR-495 / ATG14轴激活自噬,从而抑制IL-1β诱导的软骨细胞凋亡。这些发现表明hsa_circ_0005567可以用作OA的治疗靶标。hsa_circ_0005567通过调节miR-495 / ATG14轴激活自噬,从而抑制IL-1β诱导的软骨细胞凋亡。这些发现表明hsa_circ_0005567可以用作OA的治疗靶标。

更新日期:2020-08-25
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