自噬相关基因在原发性老年性骨质疏松症骨髓间充质干细胞的表达及调控作用网络研究

Expression and regulatory network of autophagy⁃related genes in mesenchymal stem cells from bone marrow of primary senile osteoporosis

目的 基于基因组芯片数据,研究自噬相关基因(ARG)在原发性老年性骨质疏松症(OP)骨髓间充质干细胞的表达水平,并探讨其在基因组的调控作用网络。方法 从GSE35959中分析原发性老年性OP骨髓间充质干细胞的差异表达基因(DEG),结合人类自噬数据库(HADb)筛选出原发性老年性OP骨髓间充质干细胞差异表达的自噬相关基因(AR-DEG),利用STRING 11.0数据库建立蛋白质-蛋白质相互作用网络(PPI),利用Network Analyst建立转录因子-基因-miRNA共表达网络和环境化学物-AR-DEGs调控网络。结果 2 866个原发性老年性OP的DEG参与了该疾病的发生发展,其中上调基因2 592个(90.44%),下调基因274个(9.56%)。获得31个原发性老年性OP的AR-DEG,均呈高表达状态。肿瘤蛋白53(TP53)、表皮生长因子受体(EGFR)、泛素C(UBC)、周期蛋白依赖激酶抑制因子1A(CDKN1A)对原发性老年性OP具有重要的生物学作用。自噬机制影响原发性老年性OP过程中,会受到转录因子、miRNA、环境因素的深度影响。结论 自噬相关基因的过表达参与了原发性老年性OP发生进展的过程,该过程与免疫功能具有一定联系,且受到多种转录因子、miRNA、微量元素和环境化学物的影响,但上述调节机制仍需要深入研究探讨。

Objective To study the expression levels of autophagy-related genes(ARGs)in mesenchymal stem cells from bone marrow of primary senile OP,and to explore its regulatory network in the genome based on the genome chip data.Methods Differentially expressed genes(DEGs)of mesenchymal stem cells from bone marrow of primary senile OP were screened from GSE35959.In combination with the human autophagy database(HADb),differentially expressed-autophagy related genes(AR-DEGs)in bone marrow mesenchymal stem cells of senile OP were screened.Then STRING 11.0 database was used to establish a protein-protein interaction(PPI)network.Transcription factor(TF)-gene-miRNA co-expression network and environmental chemicals-AR-DEGs regulatory network were established based on Network Analyst.Results A total of 2866 DEGs were involved in the development and progression of primary OP in the elderly,including 2592(90.44%)up-regulated genes and 274(9.56%)down-regulated genes.Thirty-one AR-DEGs related to primary senile OP were obtained,and they were all highly expressed.Tumor protein 53(TP53),epidermal growth factor receptor(EGFR),ubiquitin C(UBC),and cyclin deperdent kinase inhibitor 1A(CDKN1A)showed important biological effects on primary senile OP.The autophagy was deeply affected by TFs,miRNAs,and environmental factors in primary senile OP.Conclusion The overexpression of autophagy is involved in the development and progression of primary senile OP.This process is related to immune function and is affected by a variety of TFs,microRNAs,trace elements and environmental chemicals.But the regulation mechanism still needs in-depth study.