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hsa_circ_0059955 的敲低通过抑制. 诱导髓核细胞凋亡和细胞周期停滞。

Knockdown of hsa_circ_0059955 Induces Apoptosis and Cell Cycle Arrest in Nucleus Pulposus Cells via Inhibiting .

机构信息

Department of Orthopedics, China-Japan Union Hospital, Changchun, Jilin 130031, People's Republic of China.

出版信息

Drug Des Devel Ther. 2020 Sep 25;14:3951-3963. doi: 10.2147/DDDT.S253293. eCollection 2020.

Abstract

BACKGROUND

Circular RNAs (circRNAs) play an important role in the progression of intervertebral disc (IVD) degeneration (IVDD). Using bioinformatics analysis, we have found that the expression of circRNA hsa_circ_0059955 was significantly downregulated in IVDD tissues. However, the relevant mechanism of hsa_circ_0059955 in the progression of IVDD remains unclear.

METHODS

CCK-8 and flow cytometry assays were used to evaluate cell proliferation and apoptosis. In addition, Western blot assay was used to detect the expressions of ITCH, p73, CDK2 in nucleus pulposus (NP) cells. Moreover, a puncture-induced IVDD rat model was established to explore the role of hsa_circ_0059955 in IVDD.

RESULTS

The level of hsa_circ_0059955 was significantly decreased in IVDD tissues from IVDD patients. (ITCH) is the host gene of hsa_circ_0059955, and downregulation of hsa_circ_0059955 significantly decreased the expression of ITCH in NP cells. In addition, downregulation of hsa_circ_0059955 markedly inhibited proliferation and induced apoptosis and cell cycle arrest in NP cells. Moreover, in vivo study illustrated that overexpression of hsa_circ_0059955 ameliorated IVDD in rats.

CONCLUSION

Downregulation of hsa_circ_0059955 could induce apoptosis and cell cycle arrest in NP cells in vitro, while overexpression of hsa_circ_0059955 attenuated the IVDD in a puncture-induced rat model in vivo. Therefore, hsa_circ_0059955 might serve as a therapeutic target for the treatment of IVDD.

摘要

背景

环状 RNA(circRNA)在椎间盘退行性变(IVDD)的进展中发挥着重要作用。通过生物信息学分析,我们发现 hsa_circ_0059955 在 IVDD 组织中的表达显著下调。然而,hsa_circ_0059955 在 IVDD 进展中的相关机制尚不清楚。

方法

使用 CCK-8 和流式细胞术检测细胞增殖和凋亡。此外,使用 Western blot 检测核髓核(NP)细胞中 ITCH、p73、CDK2 的表达。并且,建立了穿刺诱导的 IVDD 大鼠模型,以探讨 hsa_circ_0059955 在 IVDD 中的作用。

结果

IVDD 患者的 IVDD 组织中 hsa_circ_0059955 的水平显著降低。(ITCH)是 hsa_circ_0059955 的宿主基因,下调 hsa_circ_0059955 显著降低了 NP 细胞中 ITCH 的表达。此外,下调 hsa_circ_0059955 明显抑制了 NP 细胞的增殖,并诱导了凋亡和细胞周期停滞。此外,体内研究表明,hsa_circ_0059955 的过表达改善了大鼠的 IVDD。

结论

hsa_circ_0059955 的下调可在体外诱导 NP 细胞凋亡和细胞周期停滞,而过表达 hsa_circ_0059955 可减轻体内穿刺诱导的大鼠 IVDD。因此,hsa_circ_0059955 可能成为治疗 IVDD 的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edfc/7526870/95b616e7b12c/DDDT-14-3951-g0001.jpg

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