The analysis and verification of osteoporosis associated hub genes and prediction of miRNA interactions

doi:10.11958/20220418

Abstract

Abstract:

Objective To screen hub genes and miRNA interaction in aging osteoporosis. Methods The GSE35956 gene chip data set was downloaded from GEO database, and the differentially expressed genes (Degs) in bone marrow mesenchymal stem cells were screened by R language in patients with osteoporosis. GO enrichment and KEGG pathway were analyzed in Degs using DAVID database. String database and Cytoscape software were used to analyze the protein interaction network and screen hub genes. The mirnas interacting with hub genes were predicted by Targetscan database, and the predicted mirnas were enriched by funrich database. Bone marrow mesenchymal stem cells from 3 to 4 month-old (the young group) and 18 to 20 month-old (the old group) in C57BL/6 mice were extracted and cultured. The expression levels of miRNA in bone marrow mesenchymal stem cells were verified by qPCR technique in the young and the old groups. Results A total of 982 up-regulated Degs and 99 down-regulated degs were identified in patients with osteoporosis. Degs were mainly enriched in plasma membrane adhesion molecule-mediated homologous cell adhesion and calcium ion binding, and were mainly involved in neuroactive ligand-receptor interaction signaling pathways. PPI interaction network analysis identified eight core genes: leptin (LEP), lymphocyte-specific protein tyrosine kinase (LCK), WT1 transcription factor (WT1), SRY-box transcription factor 10 (SOX10), integrin subunit beta 2 (ITGB2), albumin (ALB), cholecystokinin (CCK) and bone morphogenetic protein 7（BMP7). The interaction between 105 miRNA and 6 core genes was predicted by Trargetscan. qPCR results showed that BMP7, CCK, ITGB2 and SOX10 genes in bone marrow mesenchymal stem cells were significantly up-regulated in the old group compared with those of the young group. It is consistent with the results of bioinformatics analysis. Conclusion The expression levels of the selected core genes are related to the differentiation degree of bone marrow mesenchymal stem cells in aged mice. The identified miRNA may be a diagnostic marker and a therapeutic target for aging osteoporosis.

Key words: osteoporosis, computational biology, microRNAs, bone marrow mesenchymal stem cells, protein-protein interaction

CLC Number:

R681.4

Figures/Tables 7

References 25

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组别	BMP7	CCK	ITGB2	SOX10
青年组	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
老年组	4.24±0.31	3.93±0.38	2.08±0.25	2.92±0.46
t	23.373^＊＊	17.340^＊＊	9.650^＊＊	9.257^＊＊

组别	BMP7	CCK	ITGB2	SOX10
青年组	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
老年组	4.24±0.31	3.93±0.38	2.08±0.25	2.92±0.46
t	23.373^＊＊	17.340^＊＊	9.650^＊＊	9.257^＊＊