Integrated analysis of transcriptome and proteome to explore the genes related to steroid-induced femoral head necrosis.

Abstract

PURPOSE:

Femoral head necrosis (FHN) is a common disease of hip. However, the pathogenesis of FHN is not well understood. This study attempted to explore the potentially important genes and proteins involved in FHN.

METHODS:

We integrated the transcriptomic and proteomic methods to quantitatively screen the differentially expressed genes (DEGs) and proteins (DEPs) between Control and FHN groups. Gene ontology (GO) terms and KEGG pathway enrichment analysis were used to assess the roles of DEGs and DEPs. qRT-PCR and western blot were performed to verify the key genes/proteins in FHN. CCK-8 assay was performed to measure cell viability. The protein expression of Bax and Bcl-2 were used to evaluate cell apoptosis.

RESULTS:

Transcriptome and proteome studies indicated 758 DEGs and 1097 DEPs between Control and FHN groups, respectively. Cell division, extracellular exosome, and serine-type endopeptidase activity were the most common terms in biological process (BP), cellular component (CC), and molecular function (MF) enrichment, respectively. DEPs were mainly enriched in cellular process, cell, and binding for BP, CC, and MF categories, respectively. DEGs were mainly involved in PI3K-Akt pathway and DEPs were mainly focused in glycolysis/gluconeogenesis pathway. Notably, 14 down-regulated and 22 up-regulated genes/proteins were detected at both the transcript and protein level. LRG1, SERPINE2, STMN1, COL14A1, SLC37A2, and MMP2 were determined as the key genes/proteins in FHN. SERPINE2/STMN1 overexpression increased viability and decreased apoptosis of dexamethasone-treated MC3T3-E1 cells.

CONCLUSIONS:

Our study investigated some pivotal regulatory genes/proteins in the pathogenesis of FHN, providing novel insight into the genes/proteins involved in FHN.

• Authors: Ning Yang, Hongzhi Wang, Weicheng Zhang, Houyi Sun, Meng Li, Yaozeng Xu, Lixin Huang, Dechun Geng
• Journal: Experimental cell research (Exp Cell Res) Vol. 401 Issue 1 Pg. 112513 (04 01 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 33567325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Proteome
• Proto-Oncogene Proteins c-bcl-2
• Serpin E2
• Serpine2 protein, mouse
• Stathmin
• Steroids
• Stmn1 protein, mouse
• bcl-2-Associated X Protein
• Bcl2 protein, mouse
• Dexamethasone

Topics

• 3T3 Cells
• Animals
• Cell Survival (genetics)
• Dexamethasone (pharmacology)
• Femur Head Necrosis (chemically induced, genetics, pathology)
• Gene Expression Profiling
• Gene Expression Regulation (genetics)
• Gene Ontology
• Humans
• Mice
• Phosphatidylinositol 3-Kinases (genetics)
• Proteome (classification, genetics)
• Proteomics
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Serpin E2 (genetics)
• Stathmin (genetics)
• Steroids (toxicity)
• Transcriptome (genetics)
• bcl-2-Associated X Protein (genetics)