ABSTRACT

Intervertebral disc degeneration (IVDD) is a complicated pathological condition accompanying with low back pain. This study was designed to figure out the mechanism of lncRNA XIST in IVDD. Abnormally expressed lncRNAs in IVDD patients were measured. The correlations among XIST, miR-19 and PTEN were identified. Overexpression and silencing of XIST, miR-19 and PTEN were introduced and their roles in NPC autophagy in vitro were detected. The potential signaling pathway involved in these events was identified. Consequently, high expression of XIST was found in IVDD patients. It induced NPC autophagy and reduced NPC viability. XIST could serve as a competing endogenous RNA (ceRNA) for miR-19 and upregulate PTEN expression. The overexpression of XIST reduced miR-19 expression, which was followed by enhanced PTEN expression. Upregulation of miR-19 increased NPC viability and proliferation, while decreased NPC autophagy that regulated by XIST, while overexpressed PTEN reversed the above changes. Moreover, overexpression of XIST inactivated the PI3k/Akt signaling pathway.

摘要

椎间盘退变（IVDD）是一种伴有腰痛的复杂病理状况。本研究旨在弄清楚 IVDD 中 lncRNA XIST 的机制。测量了 IVDD 患者中异常表达的 lncRNA。确定了 XIST、miR-19 和 PTEN 之间的相关性。介绍了 XIST、miR-19 和 PTEN 的过表达和沉默及其在体外NPC 自噬中的作用被检测到。确定了参与这些事件的潜在信号通路。因此，在 IVDD 患者中发现了 XIST 的高表达。它诱导NPC自噬并降低NPC活力。XIST 可以作为 miR-19 的竞争性内源性 RNA (ceRNA) 并上调 PTEN 表达。XIST 的过表达降低了 miR-19 的表达，随后增强了 PTEN 的表达。miR-19的上调增加了NPC的活力和增殖，同时减少了由XIST调节的NPC自噬，而过表达的PTEN逆转了上述变化。此外，XIST 的过表达使 PI3k/Akt 信号通路失活。