Department of Traumatic Orthopedics, Institute of Orthopedics, Huizhou Central People's Hospital, No. 41, North E'ling Road, Huizhou, 516000, Guangdong Province, China.
J Orthop Surg Res. 2021 Jul 30;16(1):472. doi: 10.1186/s13018-021-02615-y.
Rheumatic arthritis (RA) is an autoimmune disease with bad effects. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of RA, but the mechanism still indistinct. In this work, we explored the roles of circ_0025908 in RA.
The levels of circ_0025908, microRNA-137 (miR-137), and mRNA of homeodomain-interacting protein kinase 2 (HIPK2) were detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in RA tissues. Meanwhile, the level of HIPK2 was quantified by Western blot analysis. Besides, the cell functions were examined by CCK8 assay, EdU assay, flow cytometry assay, ELISA, and Western blot. Furthermore, the interplay between miR-137 and circ_0025908 or HIPK2 was detected by dual-luciferase reporter assay.
The levels of circ_0025908 and HIPK2 were upregulated, and the miR-137 level was decreased in RA tissues in contrast to that in normal tissues. For functional analysis, circ_0025908 deficiency inhibited cell vitality, cell mitotic cycle, cell proliferation, and immunoreaction in RA cells, whereas promoted cell apoptosis. Moreover, miR-137 was confirmed to repress the progression of RA cells by suppressing HIPK2. In mechanism, circ_0025908 acted as a miR-137 sponge to regulate the level of HIPK2.
Circ_0025908 facilitates the development of RA through increasing HIPK2 expression by regulating miR-137, which also offered an underlying targeted therapy for RA treatment.
风湿性关节炎（RA）是一种具有不良影响的自身免疫性疾病。最近的研究表明，环状 RNA（circRNA）可能影响 RA 的进展，但机制仍不清楚。在这项工作中，我们探讨了 circ_0025908 在 RA 中的作用。
通过实时定量逆转录聚合酶链反应（qRT-PCR）检测 RA 组织中 circ_0025908、微小 RNA-137（miR-137）和同源结构域相互作用蛋白激酶 2（HIPK2）mRNA 的水平。同时，通过 Western blot 分析定量 HIPK2 的水平。此外，通过 CCK8 测定、EdU 测定、流式细胞术测定、ELISA 和 Western blot 检测细胞功能。此外，通过双荧光素酶报告基因检测 miR-137 与 circ_0025908 或 HIPK2 之间的相互作用。
与正常组织相比，RA 组织中 circ_0025908 和 HIPK2 的水平上调，miR-137 的水平下调。功能分析表明，circ_0025908 缺陷抑制 RA 细胞的活力、细胞有丝分裂周期、细胞增殖和免疫反应，而促进细胞凋亡。此外，miR-137 通过抑制 HIPK2 来抑制 RA 细胞的进展。在机制上，circ_0025908 通过调节 miR-137 来发挥作用，从而增加 HIPK2 的表达，促进 RA 的发展。
circ_0025908 通过调节 miR-137 增加 HIPK2 的表达，促进 RA 的发展，为 RA 的治疗提供了潜在的靶向治疗。
