Department of Rheumatology and Immunology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Endoscope Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Mol Med Rep. 2018 Feb;17(2):3312-3317. doi: 10.3892/mmr.2017.8225. Epub 2017 Dec 8.
MicroRNA-137 (miR-137) is involved in cell proliferation, migration, invasion and apoptosis in a variety of cells. However, the role of miR‑137 in rheumatoid arthritis (RA) remains unclear. The present study aimed to identify the biological roles of miR‑137 in RA. The expression of miR‑137 in RA fibroblast‑like synoviocytes (RA‑FLS) and in normal control FLS was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The effects of miR‑137 on RA‑FLS proliferation, migration and invasion were also determined using MTT, wound healing and Transwell invasion assays, respectively. The effects of miR‑137 on inflammatory cytokine expression in RA‑FLS were assessed by ELISA. Bioinformatics databases (TargetScan and miRanda), luciferase reporter assays, RT‑qPCR and western blotting assays were conducted to identify potential target genes. miR‑137 expression was decreased in RA‑FLS compared with expression in normal control FLS. Overexpression of miR‑137 resulted in a significant reduction in RA‑FLS proliferation, migration and invasion, and decreased the expression of inflammatory cytokines of RA‑FLS. In addition, bioinformatics analysis and luciferase reporter assays indicated that miR‑137 may target the 3'‑untranslated region of C‑X‑C motif chemokine ligand 12 (CXCL12), which was confirmed by RT‑qPCR and western blot analyses. These results further demonstrated that miR‑137may serve an inhibitory role in RA by targeting CXCL12 expression, and miR‑137 may be a potential target for the treatment of RA.
微小 RNA-137(miR-137)参与多种细胞的增殖、迁移、侵袭和凋亡。然而,miR-137 在类风湿关节炎(RA)中的作用尚不清楚。本研究旨在确定 miR-137 在 RA 中的生物学作用。采用逆转录-定量聚合酶链反应(RT-qPCR)检测 miR-137 在 RA 成纤维样滑膜细胞(RA-FLS)和正常对照 FLS 中的表达。采用 MTT、划痕愈合和 Transwell 侵袭实验分别检测 miR-137 对 RA-FLS 增殖、迁移和侵袭的影响。采用 ELISA 检测 miR-137 对 RA-FLS 中炎症细胞因子表达的影响。采用生物信息学数据库(TargetScan 和 miRanda)、荧光素酶报告基因实验、RT-qPCR 和 Western blot 实验鉴定潜在的靶基因。与正常对照 FLS 相比,miR-137 在 RA-FLS 中的表达降低。miR-137 的过表达导致 RA-FLS 的增殖、迁移和侵袭显著减少,同时降低 RA-FLS 中炎症细胞因子的表达。此外,生物信息学分析和荧光素酶报告基因实验表明,miR-137 可能靶向 C-X-C 基序趋化因子配体 12(CXCL12)的 3'-非翻译区,这通过 RT-qPCR 和 Western blot 分析得到了进一步证实。这些结果进一步表明,miR-137 通过靶向 CXCL12 表达在 RA 中发挥抑制作用,miR-137 可能是治疗 RA 的潜在靶点。