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               · 34  ·                           南 京    医 科 大 学 学         报                        2022年1月


               A                     The Most Enriched GO Terms((OP vs. CTRL))  B          KEGG pathway
                                developmental process
                               regulation of cell growth                       Protein export ⁃        1.929
                                         growth
                          regulation of response to stimulus
                   regulation of cellular protein metabolic process          Taste transduction ⁃     1.811
                 regulation of extrinsic apoptotic signaling pathwa...
                                       cell growth
                                  regulation of growth                   Dilated cardio myopathy ⁃  1.340
                       regulation of protein metabolic process
                        negative regulation of wound healing
                                                                          Riboflavin metabolism ⁃  1.284
                          anatomical structure development
                     negative regulation of response to wounding
                       negative regulation of receptor binding  type  Pantothenate and CoA biosynthesis ⁃  1.233
                  positive regulation of extrinsic apoptotic signali...  BP
                 negative regulation of response to external stimul...  CC
                                    heterochromatin        MF             Ovarian steroidogenesis ⁃  1.073
                            membrane⁃bounded organelle
                                   activin A complex
                                    activin complex                         GABAergic synapse ⁃  0.925
                                     nuclear lumen
                                  extracellular space                          Bile secretion ⁃  0.867
                                      nucloplasm
                     serine⁃type endopeptidase inhibitor activity
                           growth hormone receptor activity                   Insulin secretion ⁃  0.815
               high⁃affinity basic amino acid transmembrane grans...
                high⁃affinity arginine transmembrane transporter a...
                high⁃affinity lysine transmembrane transporter act...  Nicotinate and nicotinamidemetabolism⁃  0.791
                   L⁃arginine transmembrane transporter activity
                                             0  20  40  60                              0      1      2      3
                                               Number of genes                                 -lg(p_value)
                                                         A:GO;B:KEGG。
                                                   图3   差异lncRNA相关分析
                                       Figure 3 Results of differential lncRNA advanced analysis


              通 过 对 人 BMSC 的 研 究 发 现 ,下 调 lncRNA                试验等进一步探索并验证 lncRNA 对骨质疏松发病
              ENST00000502125.2 可导致 BMSC 内的碱性磷酸酶                的影响提供基础。
              染色强度明显增强,染色结节的数也显著增多,表                            [参考文献]
                                     [5]
              明细胞向成骨性细胞分化 。lncRNA H19在BMSC
                                                                [1] MATIC I,ANTUNOVIC M,BRKIC S,et al. Expression of
              成骨分化过程中表达显著,miR⁃140⁃5p表达显著降
                                                                     OCT⁃4 and SOX⁃2 in bone marrow⁃derived human mesen⁃
              低,功能分析显示lncRNA H19过度表达可抑制miR
                                                                     chymal stem cells during osteogenic differentiation[J].
              ⁃140⁃5p 表达,加速成骨 BMSC 分化,而 lncRNA H19
                                                                     Open Access Maced J Med Sci,2016,4(1):9-16
              缺失则抑制了 BMSC 的成骨分化过程,lncRNA H19                    [2] CHEN L L. Linking long noncoding RNA localization and
              可调控 BMSC 分化过程 。同样,lncRNA MEG3 的                        function[J]. Trends Biochem Sci,2016,41(9):761-772
                                   [3]
              下调能显著抑制 BMSC 的成骨能力,其过表达则能                         [3] BI H,WANG D,LIU X,et al. Long non⁃coding RNA H19
              提高 BMSC 的成骨能力,其对成骨分化的调节作用                              promotes osteogenic differentiation of human bone marrow
              可能是通过激活骨形态发生蛋白 4(BMP⁃4)来实现                             ⁃derived mesenchymal stem cells by regulating microRNA
                [6]
              的 。                                                    ⁃140⁃5p/SATB2 axis[J]. J Biosci,2020,45:56
                  本研究中,在骨质疏松模型大鼠 BMSC 内有                        [4] JIN C,JIA L,HUANG Y,et al. Inhibition of lncRNA
              116个lncRNA的表达差异具有统计学意义,占所有                             MIR31HG promotes osteogenic differentiation of human
                                                                     adipose ⁃ derived stem cells[J]. Stem Cells,2016,34
              lncRNA 基因的 2.3%,其中上调的 lncRNA 35 个,下
                                                                     (11):2707-2720
              调81个。根据GO功能分析,这些差异lncRNA主要
                                                                [5] QIU X,JIA B,SUN X,et al. The critical role of long non⁃
              参与细胞生长发育、解剖结构发育的调控、对应激
                                                                     coding RNA in osteogenic differentiation of human bone
              反应的调节、对细胞蛋白代谢过程的调控。差异                                  marrow mesenchymal stem cells[J]. Biomed Res Int,
              lncRNA 主要富集的 KEGG 信号通路包括蛋白的转                           2017,2017:5045827
              运通路、味觉的传导通路、核黄素的新陈代谢通路、                           [6] ZHUANG W Z,GE X E,YANG S J,et al. Upregulation of
              泛酸盐和辅酶A的生物合成通路与扩张型心肌病相                                 lncRNA MEG3 promotes osteogenic differentiation of
              关通路,这些通路可能间接调控骨质疏松的病理过                                 mesenchymal stem cells from multiple myeloma patients
              程,本研究结果可为后续动物体内体外实验、临床                                                             (下转第46页)
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