Comprehensive analysis of GINS subunits prognostic value and ceRNA network in sarcoma

Zhou, Chuqiao; Chen, Zhuoyuan; Xiao, Bo; Cheng, Xiang; Li, Aoyu; Zhao, Ziyue; Li, Hui

doi:10.3389/fcell.2022.951363

Cited by 4 publications

(3 citation statements)

References 70 publications

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“…In STRING based protein–protein interaction, the MCM6 protein significantly interacted with 10 different proteins 8 , 11 , 14 , 69 – 72 , 80 , 83 , 85 , 86 having the confidence score of ≥ 0.9 87 (Fig. 7 and Supplementary Table S5 ).…”

Section: Discussionmentioning

confidence: 99%

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Kamal,

Mia,

Faruque

et al. 2024

Sci Rep

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Single nucleotide polymorphisms (SNPs) are one of the most common determinants and potential biomarkers of human disease pathogenesis. SNPs could alter amino acid residues, leading to the loss of structural and functional integrity of the encoded protein. In humans, members of the minichromosome maintenance (MCM) family play a vital role in cell proliferation and have a significant impact on tumorigenesis. Among the MCM members, the molecular mechanism of how missense SNPs of minichromosome maintenance complex component 6 (MCM6) contribute to DNA replication and tumor pathogenesis is underexplored and needs to be elucidated. Hence, a series of sequence and structure-based computational tools were utilized to determine how mutations affect the corresponding MCM6 protein. From the dbSNP database, among 15,009 SNPs in the MCM6 gene, 642 missense SNPs (4.28%), 291 synonymous SNPs (1.94%), and 12,500 intron SNPs (83.28%) were observed. Out of the 642 missense SNPs, 33 were found to be deleterious during the SIFT analysis. Among these, 11 missense SNPs (I123S, R207C, R222C, L449F, V456M, D463G, H556Y, R602H, R633W, R658C, and P815T) were found as deleterious, probably damaging, affective and disease-associated. Then, I123S, R207C, R222C, V456M, D463G, R602H, R633W, and R658C missense SNPs were found to be highly harmful. Six missense SNPs (I123S, R207C, V456M, D463G, R602H, and R633W) had the potential to destabilize the corresponding protein as predicted by DynaMut2. Interestingly, five high-risk mutations (I123S, V456M, D463G, R602H, and R633W) were distributed in two domains (PF00493 and PF14551). During molecular dynamics simulations analysis, consistent fluctuation in RMSD and RMSF values, high Rg and hydrogen bonds in mutant proteins compared to wild-type revealed that these mutations might alter the protein structure and stability of the corresponding protein. Hence, the results from the analyses guide the exploration of the mechanism by which these missense SNPs of the MCM6 gene alter the structural integrity and functional properties of the protein, which could guide the identification of ways to minimize the harmful effects of these mutations in humans.

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Section: Discussionmentioning

confidence: 99%

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Kamal,

Mia,

Faruque

et al. 2024

Sci Rep

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“…The cBioPortal database was used to analyze mutations in OPA1 in tumor tissue [ 55 ]. First, we found the ‘Quick selection’ section, then clicked on ‘TCGA Pan-Cancer Atlas Study’, and then typed ‘ OPA1 ’ in the search field to query OPA1 gene alterations.…”

Section: Methodsmentioning

confidence: 99%

Multi-omics analysis of the oncogenic role of optic atrophy 1 in human cancer

Wu,

Xu,

et al. 2023

Aging

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Objective: To investigate the prognostic significance of optic atrophy 1 ( OPA1 ) in pan-cancer and analyze the relationship between OPA1 and immune infiltration in cancer. Results: OPA1 exhibited high expression levels or mutations in various types of tumor cells, and its expression levels were significantly correlated with the survival rate of tumor patients. In different tumor tissues, there was a notable positive correlation between OPA1 expression levels and the infiltration of cancer-associated fibroblasts in the immune microenvironment. Additionally, OPA1 and its related genes were found to be involved in several crucial biological processes, including protein phosphorylation, protein import into the nucleus, and protein binding. Conclusion: OPA1 is highly expressed or mutated in numerous tumors and is strongly associated with protein phosphorylation, patient prognosis, and immune cell infiltration. OPA1 holds promise as a novel prognostic marker with potential clinical utility across various tumor types. Methods: We examined OPA1 expression in pan-cancer at both the gene and protein levels using various databases, including Tumor Immune Estimation Resource 2.0 (TIMER 2.0), Gene Expression Profiling Interactive Analysis (GEPIA2), UALCAN, and The Human Protein Atlas (HPA). We utilized the Kaplan-Meier plotter and GEPIA datasets to analyze the relationship between OPA1 expression levels and patient prognosis. Through the cBioPortal database, we detected OPA1 mutations in tumors and examined their relationship with patient prognosis. We employed the TIMER 2.0 database to explore the correlation between OPA1 expression levels in tumor tissue and the infiltration of cancer-associated fibroblasts in the immune microenvironment. Furthermore, we conducted a gene search associated with OPA1 and performed enrichment analysis to identify the main signaling pathways and biological processes linked to them.

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“…The characteristic of ceRNA networks in cancer area is distinct from the normal tissue, thus the feature of ceRNA networks can be used to distinguish tumors from normal tissues, and mesenchymal stem cells ( 12 ). ceRNA networks can even be used to identify recurrent tumors from primary tumor tissues ( 13 ), and to characterize different tumor subtypes no matter base on the molecular component ( 14 ), or TME assessment ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma

Leng,

Yang,

Sun

et al. 2023

Clinical Cancer Research

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Purpose: Sarcoma is the second most common solid tumor type in children and adolescents. The high level of tumor heterogeneity as well as aggressive behavior of sarcomas brings serious difficulties to developing effective therapeutic strategies for clinical application. Therefore, it is of great importance to identify accurate biomarkers for early detection and prognostic prediction of sarcomas. Experimental Design: In this study, we characterized three subtypes of sarcomas based on tumor immune infiltration levels (TIIL), and constructed a prognosis-related competing endogenous RNA (ceRNA) network to investigate molecular regulations in the sarcoma tumor microenvironment (TME). We further built a subnetwork consisting of mRNAs and lncRNAs that are targets of key miRNAs and strongly correlated with each other in the ceRNA network. After validation using public data and experiments in vivo and in vitro, we deeply dug the biological role of the miRNAs and lncRNAs in a subnetwork and their impact on TME. Results: Altogether, 5 miRNAs (hsa-mir-125b-2, hsa-mir-135a-1, hsa-mir92a-2, hsa-mir-181a-2, and hsa-mir-214), 3 lncRNAs (LINC00641, LINC01146, and LINC00892), and 10 mRNAs (AGO2, CXCL10, CD86, CASP1, IKZF1, CD27, CD247, CD69, CCR2, and CSF2RB) in the subnetwork were identified as vital regulators to shape the TME. On the basis of the systematic network, we identified that trichostatin A, a pan-HDAC inhibitor, could potentially regulate the TME of sarcoma, thereby inhibiting the tumor growth. Conclusions: Our study identifies a ceRNA network as a promising biomarker for sarcoma. This system provides a more comprehensive understanding and a novel perspective of how ceRNAs are involved in shaping sarcoma TME.

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Comprehensive analysis of GINS subunits prognostic value and ceRNA network in sarcoma

Cited by 4 publications

References 70 publications

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene

Multi-omics analysis of the oncogenic role of optic atrophy 1 in human cancer

Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma

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