Knockdown of LINC01138 protects human chondrocytes against IL-1β-induced damage by regulating the hsa-miR-1207-5p/KIAA0101 axis

Abstract

Introduction: Long intergenic non-protein coding RNA 1138 (LINC01138) plays a vital role in human cancers. In this study, we aimed to investigate the effect of LINC01138 on the progression of osteoarthritis (OA) and explore its potential mechanism of action. Methods: The expression of LINC01138, hsa-miR-1207-5p, and KIAA0101 in OA tissues and normal tissues was analyzed using GSEA datasets and confirmed in human specimens. Human chondrocytes were treated with interleukin (IL)-1β to establish an OA cell model. Quantitative real time PCR(qRT-PCR), enzyme-linked immunosorbent assay, and western blotting analyses were performed to evaluate the role of LINC01138, hsa-miR-1207-5p, and KIAA0101 during extracellular matrix (ECM) protein degeneration and cellular inflammatory response. The target relationship was predicted using DIANA-TarBase and TargetScan. The binding effects were verified by dual-luciferase reporter assay. Results: LINC01138 expression was higher in OA tissues than in normal controls. LINC01138 levels increased in chondrocytes treated with IL-1β. Silencing of LINC01138 attenuated the IL-1β-induced decrease in Col2α1, aggrecan, and sulphated glycosaminoglycan (sGAG), and inhibited the IL-1β-induced increase in matrix metalloproteinase (MMP)-13, IL-6, and tumor necrosis factor (TNF)-α. miR-1207-5p is weakly expressed in OA tissues and cell models. The inhibition of hsa-miR-1207-5p, a target of LINC01138, attenuated the effects of LINC01138 silencing on chondrocyte ECM degeneration and inflammatory responses. Silencing KIAA0101, a target of hsa-miR-1207-5p, alleviated the effect of hsa-miR-1207-5p on chondrocyte ECM degeneration and inflammatory responses. Furthermore, silencing of KIAA0101 inhibited the JAK/STAT and Wnt signaling pathways. Conclusion: Silencing LINC01138 protected chondrocytes from IL-1β-induced damage, possibly by regulating the hsa-miR-1207-5p/KIAA0101 axis.