长链非编码 RNA MALAT1 通过海绵吸附 miR-503 在体内和体外对髓核细胞生物学表现出正向作用。

LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503.

机构信息

Department of Emergency Medical, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Department of Geriatrics, Yan' An Hospital of Kunming City, Kunming, China.

出版信息

BMC Mol Cell Biol. 2020 Mar 30;21(1):23. doi: 10.1186/s12860-020-00265-2.

BACKGROUND

Intervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects.

RESULTS

We validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro, overexpressed MALAT1 could attenuate the effect of IL-1β on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo, MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment.

CONCLUSION

Our data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.

背景

椎间盘退变（IDD）的特征是髓核细胞（NPC）丢失和表型异常。越来越多的证据表明，长非编码 RNA（lncRNA）参与了 IDD 的发病机制。在这项研究中，我们旨在研究 lncRNA MALAT1 对 IDD 中 NPC 的功能影响及其可能的作用机制。

结果

我们验证了 MALAT1 在 IDD 组织中的表达降低，这与 Collagen II 和 Aggrecan 表达降低有关。在体外，过表达 MALAT1 可以减弱 IL-1β对 NPC 增殖、凋亡和 Aggrecan 降解的影响。在体内，MALAT1 过表达可减轻 IDD 模型大鼠椎间盘退变的严重程度。我们的分子研究进一步表明，MALAT1 可以海绵吸附 miR-503，调节 miR-503 的表达，并激活下游 MAPK 信号通路。MALAT1 对 NPC 的作用部分被 miR-503 模拟物/抑制剂处理逆转/聚集。