Identification of candidate genes for myeloma-induced osteocyte death based on microarray data

Abstract

BackgroundThe study was aimed to investigate the molecular mechanisms of osteocyte death in multiple myeloma (MM) patients.MethodsGSE27372 was downloaded from Gene Expression Omnibus, including three HOB-01 (osteocyte cell line) control samples and three HOB-01 samples co-cultured with JJN3 (human MM cell line). After the differentially expressed genes (DEGs) were identified by Student’s t test method, enrichment analyses were performed for them using DAVID software. Using TRANSFAC, TSGene, and tumor-associated gene (TAG) databases, functional annotation was conducted for the DEGs. Additionally, protein-protein interaction (PPI) network and sub-network analyses were performed using STRING database and Cytoscape software.ResultsTotal 393 DEGs were identified, including 22 transcription factors (e.g., KLF4 and IRF8) and 37 TAGs. Enrichment analysis suggested that EGF, S1PR1, and NPY1R were enriched in the function of circulatory system development. EGF (degree = 31) and EGR1 (degree = 19) had high degrees and interactions in the PPI network. In the sub-network, S1PR1, C3AR1, and NPY1R could interact with each other.ConclusionsThese DEGs might participate in the osteocyte apoptosis induced by myeloma cells. These findings might provide a theoretical basis for a better understanding of the osteolysis in MM patients.

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma

“…Furthermore, it is involved in ductal carcinoma in situ progression ( 21 ). C3AR1 is a hub mRNA for multiple myeloma ( 22 ), colon cancer ( 23 ) and melanoma ( 24 ). C3AR1 may predict chemotherapy resistance and outcomes of soft tissue sarcomas ( 25 ).…”

Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation

“… 35 Tian and his colleagues demonstrated that C3AR1 might participate in the osteocyte apoptosis induced by myeloma cells. 36 The expression of the top 5 hub genes (IL1β, CXCL1, ICAM1, CCL5, and CCL4) with connectivity degrees ≥20 showed a consistent trend by qRT-PCR assay and high-throughput sequencing. Moreover, ELISA revealed that UHMWPE particles stimulated a significant increase in the levels of IL-1β, IL-2, IL-6 and TNF-α, which was consistent with a study by Terkawi et al 4 and diffusion of vitamin E to UHMWPE could reduce the secretion of these inflammatory factors.…”