Zhengzhou Orthopaedics Hospital, 450052, China.
Zhengzhou Orthopaedics Hospital, 450052, China.
Life Sci. 2020 Jan 1;240:117019. doi: 10.1016/j.lfs.2019.117019. Epub 2019 Oct 31.
Long noncoding RNA melanotransferrin antisense RNA (MFI2-AS1) plays a vital role in the development of multiple diseases. This study aimed to investigate the effect of this lncRNA on osteoarthritis progression and explore the interaction among MFI2-AS1, microRNA (miR)-130a-3p and transcription factor 4 (TCF4).
Forty-six knee osteoarthritis tissues and 28 normal samples were collected. Human chondrocytes C28/I2 cells treated by lipopolysaccharide (LPS) were used as the model of osteoarthritis. The expression levels of MFI2-AS1, miR-130a-3p and TCF4 were detected by quantitative real-time polymerase chain reaction or western blot. LPS-induced chondrocytes injury was investigated by cell viability, apoptosis, inflammatory response and extracellular matrix degradation using MTT, flow cytometry, enzyme-linked immunosorbent assay and western blot. The target association between miR-130a-3p and MFI2-AS1 or TCF4 was confirmed by luciferase reporter assay and RNA immunoprecipitation.
MFI2-AS1 expression was increased in osteoarthritis tissues and LPS-treated C28/I2 cells. Silence of MFI2-AS1 attenuated LPS-induced viability suppression, apoptosis production, inflammatory response and extracellular matrix degradation. MFI2-AS1 was validated as a decoy of miR-130a-3p and TCF4 was confirmed as a target of miR-130a-3p. miR-130a-3p overexpression inhibited LPS-induced cell injury in C28/I2 cells by decreasing TCF4 expression. Moreover, knockdown of MFI2-AS1 alleviated LPS-induced cell injury in C28/I2 cells by mediating miR-130a-3p and TCF4.
Knockdown of MFI2-AS1 increased cell viability but suppressed apoptosis, inflammatory response and extracellular matrix degradation in LPS-treated chondrocytes by increasing miR-130a-3p and decreasing TCF4, indicating a novel target for the treatment of osteoarthritis.
长链非编码 RNA 黑素转铁蛋白反义 RNA（MFI2-AS1）在多种疾病的发展中起着至关重要的作用。本研究旨在探讨该 lncRNA 对骨关节炎进展的影响，并探讨 MFI2-AS1、微小 RNA（miR）-130a-3p 和转录因子 4（TCF4）之间的相互作用。
收集 46 例膝骨关节炎组织和 28 例正常样本。用脂多糖（LPS）处理的人软骨细胞 C28/I2 细胞作为骨关节炎模型。采用实时定量聚合酶链反应或 Western blot 检测 MFI2-AS1、miR-130a-3p 和 TCF4 的表达水平。通过 MTT、流式细胞术、酶联免疫吸附试验和 Western blot 检测 LPS 诱导的软骨细胞损伤，包括细胞活力、凋亡、炎症反应和细胞外基质降解。通过荧光素酶报告基因检测和 RNA 免疫沉淀证实 miR-130a-3p 与 MFI2-AS1 或 TCF4 的靶标关联。
MFI2-AS1 在骨关节炎组织和 LPS 处理的 C28/I2 细胞中表达增加。沉默 MFI2-AS1 可减轻 LPS 诱导的细胞活力抑制、凋亡产生、炎症反应和细胞外基质降解。MFI2-AS1 被证实是 miR-130a-3p 的诱饵，而 TCF4 被证实是 miR-130a-3p 的靶标。miR-130a-3p 过表达通过降低 TCF4 表达抑制 LPS 诱导的 C28/I2 细胞损伤。此外，沉默 MFI2-AS1 通过调节 miR-130a-3p 和 TCF4 减轻 LPS 诱导的 C28/I2 细胞损伤。
沉默 MFI2-AS1 通过增加 miR-130a-3p 和降低 TCF4 来增加 LPS 处理的软骨细胞中的细胞活力，但抑制凋亡、炎症反应和细胞外基质降解，为骨关节炎的治疗提供了新的靶点。
