Upregulated miR-154 promotes ECM degradation in intervertebral disc degeneration
Upregulated miR-154 promotes ECM degradation in intervertebral disc degeneration
复制标题
DOI：
10.1002/jcb.28471
复制
发表时间：
2019-07-01
影响因子：
4
通讯作者：
Sun, Yuanliang
中科院分区：
文献类型：
--
作者：
Wang, Jingjie;Liu, Xiaoyan;Sun, Yuanliang
椎间盘退变（IDD）是全球常见的健康问题，也是导致下背痛（LBP）的主要原因。由于IDD的病因复杂，最近发现微小RNA（microRNA，miRNA）在IDD的发病过程中起重要作用。因此，本研究旨在研究miR-154的功能，这是一系列细胞活动，IDD和其他相关机制的充分记录。收集IDD患者和对照组的腰椎髓核（NP）样本。经Solexa测序和生物信息学分析，结果显示miR-154在IDD患者NP细胞中表达增加。miR-154的抑制增加了II型胶原和聚集蛋白聚糖，并降低了胶原酶-3（MMP 13）和聚集蛋白聚糖酶-1（ADAMTS 4）的mRNA表达，而miR-154的过表达逆转了NP细胞中的这种作用。此外，荧光素酶报告基因测定揭示成纤维细胞生长因子14（FGF 14）是miR-154的直接靶标，并且FGF 14的过表达导致与miR-154的抑制类似的效果。总之，结果表明miR-154参与IDD的发展，并且其作用是通过靶向FGF 14介导的。因此，miR-154可能被认为是IDD的潜在致病因素，并可能为治疗IDD的治疗靶点提供见解。
Intervertebral disc degeneration (IDD), a common global health issue, is a major cause for low back pain (LBP). Given the complex etiology of IDD, micro RNA (miRNA) recently has been demonstrated to play essential roles in the progression of IDD. Therefore, this study aims to investigate functions of the miR-154, which is well-documented in a series of cell activities, IDD, and other relevant mechanisms. Lumbar nucleus pulposus (NP) samples were collected from patients with IDD and the control group. After solexa sequencing and bioinformatical analysis, the results showed that miR-154 was increased in NP cells of patients with IDD. Inhibition of miR-154 increased type II collagen and aggrecan and decreased mRNA expressions of collagenase-3 (MMP13) and aggrecanase-1 (ADAMTS4), whereas overexpression of miR-154 reversed such effects in NP cells. In addition, the luciferase reporter assay revealed that fibroblast growth factor 14 (FGF14) is a direct target of miR-154 and that the overexpression of FGF14 leads to similar effects as inhibition of miR-154 did. In conclusion, the results suggested that miR-154 participates in the development of IDD and its effects are mediated via targeting FGF14. Thus, miR-154 may be thought as a potential etiological factor for IDD and may provide insights into a therapeutic target to treat IDD.