Long non-coding RNAs (lncRNAs) has become a vital regulator in the pathogenesis of osteoporosis (OP). This study aimed to investigate the role of lncRNA DLEU2 in the development of proliferation and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs). High-throughput sequencing in bone tissues from 3 pairs of healthy donors and OP patients was used to search for differential lncRNAs. The expression of DLEU2 was also verified in bone tissues. The hBMSCs were transfected with DLEU2 ASO. Cell viability was detected suing MTT. Cell proliferation was determined using colony formation and EdU assays. Cell cycle and apoptosis was detected using flow cytometry. RIP, RNA pulldown, and Co-IP assays were carried out to verify the interaction between protein and protein/RNA. The binding sites between GFI1 and the promoter of DLEU2 was verified using ChIP and luciferase assays. DLEU2 expression was down-regulated in OP patients. Knockdown of DLEU2 expression significantly inhibited proliferation and promoted apoptosis of hBMSCs. Moreover, DLEU2 could interact with EZH2 to induce the activation of GFI1. Additionally, GFI1 transcriptionally activated DLEU2. Taken together, DLEU2/EZH2/GFI1 axis suppressed proliferation and enhanced hBMSC apoptosis. This may provide novel strategy for OP.

中文翻译：

---

DLEU2/EZH2/GFI1轴调控人骨髓间充质干细胞的增殖和凋亡

长链非编码RNA（lncRNA）已成为骨质疏松症（OP）发病机制的重要调节因子。本研究旨在探讨lncRNA DLEU2在人骨髓间充质干细胞（hBMSCs）增殖和凋亡过程中的作用。对 3 对健康捐献者和 OP 患者的骨组织进行高通量测序，以寻找差异性 lncRNA。DLEU2的表达也在骨组织中得到验证。hBMSC 用 DLEU2 ASO 转染。使用MTT检测细胞活力。使用集落形成和 EdU 测定来确定细胞增殖。使用流式细胞术检测细胞周期和凋亡。进行 RIP、RNA Pulldown 和 Co-IP 测定以验证蛋白质和蛋白质/RNA 之间的相互作用。使用 ChIP 和荧光素酶测定验证 GFI1 和 DLEU2 启动子之间的结合位点。OP 患者中 DLEU2 表达下调。DLEU2表达的敲低显着抑制hBMSCs的增殖并促进其凋亡。此外，DLEU2 可以与 EZH2 相互作用，诱导 GFI1 的激活。此外，GFI1 转录激活 DLEU2。总的来说，DLEU2/EZH2/GFI1 轴抑制增殖并增强 hBMSC 凋亡。这可能为OP提供新颖的策略。