The role of lncRNA XIST/miR-211 axis in modulating the proliferation and apoptosis of osteoarthritis chondrocytes through CXCR4 and MAPK signaling
The role of lncRNA XIST/miR-211 axis in modulating the proliferation and apoptosis of osteoarthritis chondrocytes through CXCR4 and MAPK signaling
复制标题
DOI：
10.1016/j.bbrc.2018.07.015
复制
发表时间：
2018-09-18
影响因子：
3.1
通讯作者：
Kuang, Lei
中科院分区：
文献类型：
--
作者：
Li, Lei;Lv, Guohua;Kuang, Lei
长非编码RNA(LncRNAs)参与多种不同的疾病，包括骨关节炎(OA)。在这里，我们探索了lncRNA XIST在骨性关节炎中的作用，并确定了可能的分子机制。XIST在骨性关节炎患者软骨组织中的表达显著上调。Xist基因敲除能显著抑制IL-1β抑制的骨性关节炎软骨细胞增殖，促进IL-1β诱导的细胞凋亡。通过使用在线工具，选择了与软骨细胞凋亡的主要贡献者CXCR4和XIST相关的miRNAs。IL-1β刺激可显著抑制MIR-211的表达，而miR-211负性调节XIST的表达和CXCR4的蛋白水平。通过直接结合，XIST作为miR-211的CERNA，对抗miR-211介导的CXCR4抑制，从而通过下游的MAPK信号调节软骨细胞的增殖和凋亡。在骨关节炎组织中，miR-211的表达显著下调，而CXCR4的mRNA表达显著上调。在组织标本中，MIR-211与XIST、CXCR4分别呈负相关，而XIST与CXCR4呈正相关。综上所述，本研究揭示了lncRNA XIST可通过miR-211/CXCR4轴促进骨性关节炎软骨细胞增殖和促进细胞凋亡。因此，lncRNA XIST可能被认为是治疗骨性关节炎的潜在靶点。(C)2018 Elsevier Inc.保留所有权利。
Long noncoding RNAs (lncRNAs) participate in multiple diverse diseases, including osteoarthritis (OA). Here, we explored the role of lncRNA XIST in OA and identified the potential molecular mechanisms. The expression of XIST in cartilage samples in patients with OA was significantly upregulated. XIST knockdown remarkably suppressed IL-1 beta-suppressed OA chondrocyte proliferation while promoted IL-1 beta-induced cell apoptosis. By employing online tools, miRNAs related to CXCR4, a major contributor to chondrocyte apoptosis, and XIST were selected. miR-211 expression could be significantly inhibited by IL-1 beta stimulation, and miR-211 negatively regulated XIST expression and CXCR4 protein levels. Through direct binding, XIST served as a ceRNA for miR-211 to counteract miR-211-mediated CXCR4 repression, thereby modulating chondrocyte proliferation and apoptosis through downstream MAPK signaling. In OA tissues, miR-211 expression was significantly downregulated while CXCR4 mRNA expression was upregulated. miR-211 was negatively correlated with XIST and CXCR4, respectively, while XIST and CXCR4 was positively correlated in tissue samples. In conclusion, the study revealed that lncRNA XIST can promote the proliferation of OA chondrocytes and promote apoptosis through the miR-211/CXCR4 axis. Thus, lncRNA XIST might be considered as a potential therapeutic target for OA treatment. (C) 2018 Elsevier Inc. All rights reserved.