Identification of Hub Genes to Regulate Breast Cancer Spinal Metastases by Bioinformatics Analyses

He, Yongxiong; Cao, Yongfei; Wang, Xiaolei; Jisiguleng, Wu; Tao, Mingkai; Liu, Jianfeng; Wang, Fei; Chao, Lemeng; Wang, Wenjun; Li, Pengfei; Fu, Haiping; Xing, Wei; Zhu, Zhibo; Huan, Yanqiang; Hu, Yuan

doi:10.1155/2021/5548918

Cited by 7 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous literature suggests that, both in vitro and in vivo , paeoniflorin regulates the migration and invasion of breast cancer cells by down-regulating microrNA-15B through FOXO1/CCND1/β-catenin axis ( 6 ). Previous studies have also indicated that CEP55 was a key regulator in BC spinal metastases by Bioinformatics Analyses ( 11 ). Despite the significant developments and rapid progression in the field of BC with bone metastasis, translation of this information into early detection markers and effective treatments are limited.…”

Section: Introductionmentioning

confidence: 92%

Identification of hub genes for early detection of bone metastasis in breast cancer

Zhao

Yang

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundGlobally, among all women, the most frequently detected and diagnosed and the most lethal type of cancer is breast cancer (BC). In particular, bone is one of the most frequent distant metastases 24in breast cancer patients and bone metastasis arises in approximately 80% of advanced patients. Thus, we need to identify and validate early detection markers that can differentiate metastasis from non-metastasis breast cancers.MethodsGSE55715, GSE103357, and GSE146661 gene expression profiling data were downloaded from the GEO database. There was 14 breast cancer with bone metastasis samples and 8 breast cancer tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). The volcano plots, Venn diagrams, and annular heatmap were generated by using the ggplot2 package. By using the cluster Profiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, K-M survival and ROC curves were generated to validate hub gene expression.ResultsBy GO enrichment analysis, 143 DEGs were enriched in the following GO terms: extracellular structure organization, extracellular matrix organization, leukocyte migration class II protein complex, collagen tridermic protein complex, extracellular matrix structural constituent, growth factor binding, and platelet-derived growth factor binding. In the KEGG pathway enrichment analysis, DEGs were enriched in Staphylococcus aureus infection, Complement and coagulation cascades, and Asthma. By PPI network analysis, we selected the top 10 genes, including SLCO2B1, STAB1, SERPING1, HLA-DOA, AIF1, GIMAP4, C1orf162, HLA-DMB, ADAP2, and HAVCR2. By using TCGA and THPA databases, we validated 2 genes, SERPING1 and GIMAP4, that were related to the early detection of bone metastasis in BC.Conclusions2 abnormally expressed hub genes could play a pivotal role in the breast cancer with bone metastasis by affecting bone homeostasis imbalance in the bone microenvironment.

show abstract

Section: Introductionmentioning

confidence: 92%

Identification of hub genes for early detection of bone metastasis in breast cancer

Zhao

Yang

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…In an ovarian cancer research, the overexpression of IFI6 could facilitate the multiplication of tumor cells and mediate their chemoresistance [ 15 ]. In addition, IFI6 is regarded as a crucial predictor of poor outcome in breast cancer [ 34 , 38 ]. In the study of hematological tumors, aberrantly expressed IFI6 in multiple myeloma is an important factor leading to the chemoresistance of myeloma cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

BM-MSCs display altered gene expression profiles in B-cell acute lymphoblastic leukemia niches and exert pro-proliferative effects via overexpression of IFI6

Pan,

Hu,

Liu

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Background The tumor microenvironment (TME) is a supportive environment responsible for promoting the growth and proliferation of tumor cells. Current studies have revealed that the bone marrow mesenchymal stem cells (BM-MSCs), a type of crucial stromal cells in the TME, can promote the malignant progression of tumors. However, in the adult B-cell acute lymphoblastic leukemia (B-ALL) microenvironment, it is still uncertain what changes in BM-MSCs are induced by leukemia cells. Methods In this study, we mimicked the leukemia microenvironment by constructing a BM-MSC–leukemia cell co-culture system. In vitro cell experiments, in vivo mouse model experiments, lentiviral transfection and transcriptome sequencing analysis were used to investigate the possible change of BM-MSCs in the leukemia niche and the potential factors in BM-MSCs that promote the progression of leukemia. Results In the leukemia niche, the leukemia cells reduced the MSCs' capacity to differentiate towards adipogenic and osteogenic subtypes, which also promoted the senescence and cell cycle arrest of the MSCs. Meanwhile, compared to the mono-cultured MSCs, the gene expression profiles of MSCs in the leukemia niche changed significantly. These differential genes were enriched for cell cycle, cell differentiation, DNA replication, as well as some tumor-promoting biofunctions including protein phosphorylation, cell migration and angiogenesis. Further, interferon alpha-inducible protein 6 (IFI6), as a gene activated by interferon, was highly expressed in leukemia niche MSCs. The leukemia cell multiplication was facilitated evidently by IFI6 both in vitro and in vivo. Mechanistically, IFI6 might promote leukemia cell proliferation by stimulating SDF-1/CXCR4 axis, which leads to the initiation of downstream ERK signaling pathway. As suggested by further RNA sequencing analysis, the high IFI6 level in MSCs somewhat influenced the gene expression profile and biological functions of leukemia cells. Conclusions BM-MSCs in the leukemia niche have varying degrees of changes in biological characteristics and gene expression profiles. Overexpression of IFI6 in BM-MSCs could be a key factor in promoting the proliferation of B-ALL cells, and this effect might be exerted through the SDF-1/CXCR4/ERK signal stimulation. Targeting IFI6 or related signaling pathways might be an important measure to reduce the leukemia cell proliferation.

show abstract

“…Hub genes of the four common signaling pathways were analyzed and WNT1, AKT3, DVL1, CCND1, HIST1H2BO, JUN, EGFR, RAC1, ACTN1 and ACTN2 were screened out. These hub genes are primarily involved in the processes of cell proliferation and differentiation (24)(25)(26)(27)(28)(29)(30)(31). Some genes are also reported to be involved in the formation of osteoclasts (32,33).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis

Zhang

Wan

et al. 2022

Exp Ther Med

View full text Add to dashboard Cite

Postmenopausal osteoporosis (PMO) is an aging-associated disease that manifests as degradation of bone tissue microstructure leading to decreased bone mass and increased bone fragility. Differentiation of peripheral blood mononuclear cells into osteoclasts is an important process in the development of PMO and identification of key genes that drive differentiation is essential to reveal the mechanism of PMO. The present study combined bioinformatics analysis of a Gene Expression Omnibus dataset of PMO and drug (bisphosphonate) target prediction using the STITCH database to identify hub genes in patients with PMO. Next, the expression of candidate hub genes was assessed in osteoclasts differentiated from THP-1 cells and small interfering RNA assays were performed to assess the function of selected hub genes. The present study identified 10 hub genes including WNT1, AKT3 , disheveled segment polarity protein 1, cyclin D1, H2B clustered histone 17, JUN, EGFR, RAC1 , actinin α1 (ACTN1) and ACTN2 . Among these, AKT3 and RAC1 were highly upregulated during osteoclast differentiation, and knockdown of AKT3 and RAC1 using small interfering RNA enhanced the inhibitory effect of bisphosphonates on osteoclast differentiation and apoptosis of monocytes as assessed by tartrate-resistant acid phosphatase staining and flow cytometry examining Annexin V-FITC/PI staining, respectively. In conclusion, AKT3 and RAC1 were key for development of PMO and inhibiting AKT3 and RAC1 may improve the therapeutic efficacy of bisphosphonates.

show abstract

Identification of Hub Genes to Regulate Breast Cancer Spinal Metastases by Bioinformatics Analyses

Cited by 7 publications

References 30 publications

Identification of hub genes for early detection of bone metastasis in breast cancer

Identification of hub genes for early detection of bone metastasis in breast cancer

BM-MSCs display altered gene expression profiles in B-cell acute lymphoblastic leukemia niches and exert pro-proliferative effects via overexpression of IFI6

Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis

Contact Info

Product

Resources

About