Identification of key regulators in parathyroid adenoma using an integrative gene network analysis

Imam, Nikhat; Alam, Aftab; Siddiqui, Mohd Faizan; Ahmed, Mohd Murshad; Malik, Md. Zubbair; Khan, Jawed; Ishrat, Romana

doi:10.6026/97320630016910

Cited by 3 publications

(1 citation statement)

References 64 publications

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“…CAV1 is a powerful negative regulator of several mitogenic signaling pathways. CAV1 downregulation in parathyroid tissue may contribute to increased activity of cyclin D1, which is involved in the pathogenesis of a greater proportion of PAs [31] . CAV1 expression was found to be upregulated in all three differentiated thyroid cancer cell lines studied by Shankar Jay et al [32] .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma

Lin

Mou

et al. 2023

Horm Metab Res

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Recent studies have demonstrated the close relationship between parathyroid adenoma(PA) and thyroid follicular adenoma(FTA). However, the underlying pathogenesis remains unknown. This study focused on exploring common pathogenic genes, as well as the pathogenesis of these two diseases, through bioinformatics methods. This work obtained PA and FTA datasets from the Integrated Gene Expression Database to identify the common differentially expressed genes (DEGs) of two diseases. The functions of the genes were investigated by GO and KEGG enrichment. The program CytoHubba was used to select the hub genes, while receiver operating characteristic curves were plotted to evaluate the predictive significance of the hub genes. The DGIbd database was used to identify gene-targeted drugs. This work detected a total of 77 DEGs. Enrichment analysis demonstrated that DEGs had activities of 3’,5'-cyclic AMP, and nucleotide phosphodiesterases and were associated with cell proliferation. NOS1, VWF, TGFBR2, CAV1, and MAPK1 were identified as hub genes after verification. The area under the curve of PA and FTA was > 0.7, and the hub genes participated in the Relaxin Signaling Pathway, focal adhesion, and other pathways. The construction of the mRNA-miRNA interaction network yielded 11 important miRNAs, while gene-targeting drug prediction identified four targeted drugs with possible effects. This bioinformatics study demonstrated that cell proliferation and tumor suppression, the hub genes co-occurring in PA and FTA, have important effects on the occurrence and progression of two diseases, which make them potential diagnostic biomarkers and therapeutic targets.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma

Lin

Mou

et al. 2023

Horm Metab Res

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Network-medicine approach for the identification of genetic association of parathyroid adenoma with cardiovascular disease and type-2 diabetes

Imam

Alam

Siddiqui

et al. 2023

Briefings in Functional Genomics

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Primary hyperparathyroidism is caused by solitary parathyroid adenomas (PTAs) in most cases (⁓85%), and it has been previously reported that PTAs are associated with cardiovascular disease (CVD) and type-2 diabetes (T2D). To understand the molecular basis of PTAs, we have investigated the genetic association amongst PTAs, CVD and T2D through an integrative network-based approach and observed a remarkable resemblance. The current study proposed to compare the PTAs-associated proteins with the overlapping proteins of CVD and T2D to determine the disease relationship. We constructed the protein–protein interaction network by integrating curated and experimentally validated interactions in humans. We found the $11$ highly clustered modules in the network, which contain a total of $13$ hub proteins (TP53, ESR1, EGFR, POTEF, MEN1, FLNA, CDKN2B, ACTB, CTNNB1, CAV1, MAPK1, G6PD and CCND1) that commonly co-exist in PTAs, CDV and T2D and reached to network’s hierarchically modular organization. Additionally, we implemented a gene-set over-representation analysis over biological processes and pathways that helped to identify disease-associated pathways and prioritize target disease proteins. Moreover, we identified the respective drugs of these hub proteins. We built a bipartite network that helps decipher the drug–target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drug combinations or drug-repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs and give a synergistic effect with better outcomes. This network-based analysis opens a new horizon for more personalized treatment and drug-repurposing opportunities to investigate new targets and multi-drug treatment and may be helpful in further analysis of the mechanisms underlying PTA and associated diseases.

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The biology of SCUBE

et al. 2023

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The SCUBE [Signal peptide-Complement C1r/C1s, Uegf, Bmp1 (CUB)-Epithelial growth factor domain-containing protein] family consists of three proteins in vertebrates, SCUBE1, 2 and 3, which are highly conserved in zebrafish, mice and humans. Each SCUBE gene encodes a polypeptide of approximately 1000 amino acids that is organized into five modular domains: (1) an N-terminal signal peptide sequence, (2) nine tandem epidermal growth factor (EGF)-like repeats, (3) a large spacer region, (4) three cysteine-rich (CR) motifs, and (5) a CUB domain at the C-terminus. Murine Scube genes are expressed individually or in combination during the development of various tissues, including those in the central nervous system and the axial skeleton. The cDNAs of human SCUBE orthologs were originally cloned from vascular endothelial cells, but SCUBE expression has also been found in platelets, mammary ductal epithelium and osteoblasts. Both soluble and membrane-associated SCUBEs have been shown to play important roles in physiology and pathology. For instance, upregulation of SCUBEs has been reported in acute myeloid leukemia, breast cancer and lung cancer. In addition, soluble SCUBE1 is released from activated platelets and can be used as a clinical biomarker for acute coronary syndrome and ischemic stroke. Soluble SCUBE2 enhances distal signaling by facilitating the secretion of dual-lipidated hedgehog from nearby ligand-producing cells in a paracrine manner. Interestingly, the spacer regions and CR motifs can increase or enable SCUBE binding to cell surfaces via electrostatic or glycan-lectin interactions. As such, membrane-associated SCUBEs can function as coreceptors that enhance the signaling activity of various serine/threonine kinase or tyrosine kinase receptors. For example, membrane-associated SCUBE3 functions as a coreceptor that promotes signaling in bone morphogenesis. In humans, SCUBE3 mutations are linked to abnormalities in growth and differentiation of both bones and teeth. In addition to studies on human SCUBE function, experimental results from genetically modified mouse models have yielded important insights in the field of systems biology. In this review, we highlight novel molecular discoveries and critical directions for future research on SCUBE proteins in the context of cancer, skeletal disease and cardiovascular disease.

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Identification of key regulators in parathyroid adenoma using an integrative gene network analysis

Cited by 3 publications

References 64 publications

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma

Network-medicine approach for the identification of genetic association of parathyroid adenoma with cardiovascular disease and type-2 diabetes

The biology of SCUBE

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