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敲低 LINC01138 通过调控 hsa-miR-1207-5p/KIAA0101 轴保护人软骨细胞免受 IL-1β诱导的损伤。

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

机构信息

Three Departments of Knee Injury, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Luoyang, Henan, P. R. China.

Department of Orthopedics, Sun Si Miao Hospital of Beijing University of Chinese Medicine, Tongchuan Traditional Chinese Medicine Hospital, Tongchuan, Shanxi, P. R. China.

出版信息

Immun Inflamm Dis. 2023 Jan;11(1):e744. doi: 10.1002/iid3.744.

DOI:10.1002/iid3.744

PMID:36705420

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9753829/

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.

摘要

简介

长链非编码 RNA 1138（LINC01138）在人类癌症中发挥着重要作用。在这项研究中，我们旨在探讨 LINC01138 对骨关节炎（OA）进展的影响，并探讨其潜在的作用机制。

方法

使用 GSEA 数据集分析 OA 组织和正常组织中 LINC01138、hsa-miR-1207-5p 和 KIAA0101 的表达，并在人标本中进行验证。用白细胞介素（IL）-1β处理人软骨细胞建立 OA 细胞模型。通过定量实时 PCR（qRT-PCR）、酶联免疫吸附试验和 Western blot 分析评估 LINC01138、hsa-miR-1207-5p 和 KIAA0101 在细胞外基质（ECM）蛋白降解和细胞炎症反应中的作用。通过 DIANA-TarBase 和 TargetScan 预测靶标关系。通过双荧光素酶报告基因实验验证结合效应。

结果

OA 组织中 LINC01138 的表达高于正常对照组。IL-1β 处理的软骨细胞中 LINC01138 水平升高。沉默 LINC01138 可减弱 IL-1β 诱导的 Col2α1、聚集蛋白聚糖和硫酸糖胺聚糖（sGAG）减少，并抑制 IL-1β 诱导的基质金属蛋白酶（MMP）-13、白细胞介素（IL）-6 和肿瘤坏死因子（TNF）-α增加。miR-1207-5p 在 OA 组织和细胞模型中表达较弱。LINC01138 的靶标 hsa-miR-1207-5p 的抑制可减弱 LINC01138 沉默对软骨细胞 ECM 降解和炎症反应的影响。沉默 hsa-miR-1207-5p 的靶标 KIAA0101 可减轻 hsa-miR-1207-5p 对软骨细胞 ECM 降解和炎症反应的影响。此外，沉默 KIAA0101 抑制了 JAK/STAT 和 Wnt 信号通路。