Bioinformatics Analysis of Key Genes and Pathways for Medulloblastoma as a Therapeutic Target

Aghamaleki, Fateme Shaanbanpour; Mollashahi, Behrouz; Aghamohammadi, Nika; Rostami, Nematollah; Mazloumi, Zeinab; Mirzaei, Hamidreza; Moradi, Abdolvahab; Sheikhpour, Mojgan; Movafagh, Abolfazl

doi:10.31557/apjcp.2019.20.1.221

Cited by 4 publications

(3 citation statements)

References 42 publications

(38 reference statements)

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“…Feng et al investigated poor prognosis-related genes of ovarian cancer by bioinformatics analysis and found that these genes were mainly enriched in the cell cycle pathway (27). It has also been reported that the cell cycle pathway is the key signaling pathway for 8 target therapy of neuroblastomas (28). Zhang et al reported that LncRNA CASC11 promoted the proliferation, migration, and invasion of GC cells in vitro via the cell cycle pathway (29).…”

Section: Discussionmentioning

confidence: 99%

Upregulated expression of SAC3D1 is associated with progression in gastric cancer

et al. 2020

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SAC3 domain containing 1 (SAC3D1) has been reported to be involved in numerous types of cancer. However, the role of SAC3D1 in GC has not yet been elucidated. In the present study, the mRNA expression level of SAC3D1 between GC and normal tissues were assessed with a continuous variable meta-analysis based on multiple datasets from public databases. The protein expression level of SAC3D1 in GC and normal tissues was assessed by an in-house immunohistochemistry (IHC). The association between SAC3D1 expression and some clinical parameters was assessed based on the TCGA and IHC data. Survival analysis was performed to assess the association between SAC3D1 expression and the survival of GC patients. The co-expressed genes of SAC3D1 were determined by integrating three online tools, and the enrichment analyses were performed to determine SAC3D1-related pathways and hub co-expressed genes. SAC3D1 was significantly upregulated in GC tumor tissues in comparison to normal tissues with the SMD being 0.45 (0.12, 0.79). The IHC results also indicated that SAC3D1 protein expression in GC tissues was markedly higher than in normal tissues. The SMD following the addition of the IHC data was 0.59 (0.11, 1.07). The protein levels of SAC3D1 were positively associated with the histological grade, T stage and N stage of GC (P<0.001). The TCGA data also revealed that the SAC3D1 mRNA level was significantly associated with the N stage (P<0.001). Moreover, prognosis analysis indicated that SAC3D1 was closely associated with the prognosis of patients with GC. Moreover, 410 co-expressed genes of SAC3D1 were determined, and these genes were mainly enriched in the cell cycle. In total, 4 genes (CDK1, CCNB1, CCNB2 and CDC20) were considered key co-expressed genes. On the whole, these findings demonstrate that SAC3D1 is highly expressed in GC and may be associated with the progression of GC.

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Section: Discussionmentioning

confidence: 99%

Upregulated expression of SAC3D1 is associated with progression in gastric cancer

et al. 2020

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“…However, most gene chip data is a mixture of both MB and glioma and does not accurately represent changes in MB, and therefore does not generate satisfactory results. There have been reports of microarray data to find DEGs in medulloblastoma (Shaabanpour Aghamaleki et al, 2019). However, the reliability of the analysis results was controversial due to the heterogeneity of the sample from a single cohort study.…”

Section: Introductionmentioning

confidence: 99%

Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses

Liu

Zhang

Sun

et al. 2020

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Background Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB. Methods Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap. Result We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB. Conclusion In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.

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“…Isochromosome 17q and KCNA1 function as immunohistochemical markers that are seen in group 4 of medulloblastoma [14]. Furthermore, several protein-coding genes mutation and expression modification are seen in medulloblastoma patients that act as medulloblastoma pathogenesis [15]. There are other existing mechanisms that control gene expressions, such as, noncoding RNAs like microRNAs (miRNAs) and lncRNAs, DNA methylation and histone modifications.…”

Section: Introductionmentioning

confidence: 99%

The Roles of miRNAs in Medulloblastoma: A Systematic Review

2019

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Medulloblastoma is considered one of the most threatening malignant brain tumors with an extremely high mortality rate in children. In the medulloblastoma, there are several genes and mutations found to work in an unregulated manner that works together to push the cells into a cancerous state. With the discovery of non-coding RNAs such as microRNAs (miRNAs), it has been shown that a different layer of gene regulations may be disrupted which would cause cancer. This fact led scientists to put their focus on the role of miRNAs in cancer. A mature miRNA contains a seed sequence which gives the miRNA to identify and attach to the interest mRNA; this attachment may lead degradation of mRNA or suppress of translation of the mRNA. The expression of miRNAs in medulloblastoma shows that some of these non-coding RNAs are overexpressed (OncomiRs) which help cells to proliferate and keep their stemness features. On the other hand, there are other forms of these miRNAs which normally inhibit cell proliferation and promote cell differentiation (tumor suppressor). These are down-regulated during cancer progression. In this systematic review, we attempted to gather several important studies on miRNAs’ role in medulloblastoma tumors and the importance of these non-coding RNAs in the future study of cancer.

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Bioinformatics Analysis of Key Genes and Pathways for Medulloblastoma as a Therapeutic Target

Cited by 4 publications

References 42 publications

Upregulated expression of SAC3D1 is associated with progression in gastric cancer

Upregulated expression of SAC3D1 is associated with progression in gastric cancer

Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses

The Roles of miRNAs in Medulloblastoma: A Systematic Review

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