Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):461-471. doi: 10.26355/eurrev_201801_14196.
Several microRNAs have been reported to contribute the progression of rheumatoid arthritis (RA) due to the ectopic expression of miRNAs in fibroblast-like synoviocytes (FLS). However, the function of miR-212-3p in RA still has not been mentioned before.
We obtained serum, synovial tissues, and FLS samples from RA patients and normal donors. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to analysis the expression level of miR-212-3p. By using miR-212-3p mimics and inhibitors, we detected the effects of miR-212-3p on cell proliferation, cell cycle, and apoptosis in RA-FLS. Dual-luciferase and Western-blot were employed to verify the target of miR-212-3p. In addition, we over-expressed the SOX5 in miR-212-3p mimics treatment FLS to emphasize our results.
The level of miR-212-3p in serum, synovial tissues, and FLS from RA patients was lower than these in relative normal group. Up-regulation of miR-212-3p inhibited cell proliferation, promoted cell apoptosis; however, knockdown of miR-212-3p promoted cell growth but reduced cell apoptotic rate. Furthermore, we found SOX5 as a direct target of miR-212-3p in RA-FLS and up-regulation of SOX5 reversed the effects of miR-212-3p over-expression.
miR-212-3p could reduce cell proliferation and promoted cell apoptosis of RA-FLS via repressing SOX5, which may provide a new biological target for RA treatment.
由于 miRNA 在成纤维样滑膜细胞(FLS)中的异位表达,已有几种 miRNA 被报道有助于类风湿关节炎(RA)的进展。然而,miR-212-3p 在 RA 中的功能尚未被提及。
我们从 RA 患者和正常供体中获得血清、滑膜组织和 FLS 样本。定量实时聚合酶链反应(qRT-PCR)用于分析 miR-212-3p 的表达水平。通过使用 miR-212-3p 模拟物和抑制剂,我们检测了 miR-212-3p 对 RA-FLS 细胞增殖、细胞周期和细胞凋亡的影响。双荧光素酶和 Western blot 用于验证 miR-212-3p 的靶标。此外,我们在 miR-212-3p 模拟物处理的 FLS 中转染 SOX5 过表达质粒以强调我们的结果。
RA 患者血清、滑膜组织和 FLS 中的 miR-212-3p 水平低于相对正常组。miR-212-3p 的上调抑制细胞增殖,促进细胞凋亡;然而,miR-212-3p 的下调促进细胞生长但降低细胞凋亡率。此外,我们发现 SOX5 是 RA-FLS 中 miR-212-3p 的直接靶标,SOX5 的上调逆转了 miR-212-3p 过表达的作用。
miR-212-3p 通过抑制 SOX5 减少 RA-FLS 的细胞增殖并促进细胞凋亡,这可能为 RA 治疗提供新的生物学靶点。