MELK is a prognostic biomarker and correlated with immune infiltration in glioma

Yang, Haiyan; Zhou, Huandi; Wang, Guohui; Tian, Lei; Li, Haonan; Zhang, Yufeng; Xue, Xiaoying

doi:10.3389/fneur.2022.977180

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…Among these genes, high expression of MELK is measured to predict poor survival in glioma and significantly correlated with higher fractions of immunocytes such as T cells, macrophages and neutrophils. 24 CEP55 is also highly expressed in endometrial cancer and directly linked to the patients' poor prognosis. 25 In a variety of malignancies, the histone methyl transferase EZH2 has pro-oncogenic and immunomodulatory effects.…”

Section: Discussionmentioning

confidence: 99%

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

Liu,

Xie,

et al. 2024

The FASEB Journal

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BackgroundCervical cancer (CC), closely linked to persistent human papillomavirus infection, represents a major health problem for women worldwide. The objective of this study is to elucidate KIF23's role in the development of CC and its regulatory mechanism.MethodsThe bioinformatics methods were utilized to extract pyroptosis‐associated differentially expressed genes (DEGs) and pivot genes from the GSE9750 and GSE63678 datasets, followed by immune infiltration analysis and quantification of these genes' expression. The effects of kinesin family member 23 (KIF23) were verified through functional experiments in vitro and a mouse xenograft model. The NLPR3 activator, nigericin, was applied for further analyzing the potential regulatory mechanism of KIF23 in CC.ResultsA total of 8 pyroptosis‐related DEGs were screened out, among which 4 candidate core genes were identified as candidate hub genes and confirmed upregulation in CC tissues and cells. These genes respectively showed a positive correlation with the infiltration of distinct immune cells or tumor purity. Downregulation of KIF23 could suppress the proliferation, migration, and invasion abilities in CC cells and tumorigenesis through enhancing pyroptosis. Conversely, KIF23 overexpression accelerated the malignant phenotypes of CC cells and inhibited pyroptosis activation, which was blocked by nigericin treatment.ConclusionsKIF23 may play an oncogenic role in CC progression via inhibition of the NLRP3‐mediated pyroptosis pathway.

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Section: Discussionmentioning

confidence: 99%

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

Liu,

Xie,

et al. 2024

The FASEB Journal

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“…MELK (maternal embryonic leucine zipper kinase) was elevated in glioma tissues and associated with poorer survival. DDOST induced the tumor immunosuppressive microenvironment in gliomas [ 43 ]. The TME is the cellular environment in which tumor cells reside, and its composition includes extracellular matrix, soluble molecules, and tumor stromal cells [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer

Mei,

Pan,

Huang

et al. 2024

Discov Onc

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Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.

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“…One of these modules contained the "MELK" gene and the other contained the "FBXO5" gene. Both MELK and FBXO5 are heavily associated with cancer [30][31][32][33] in general and glioma in particular [34][35][36][37][38][39] . Using the previous RNA-seq data we analyzed which of the twelve compounds was most effective at reducing expression of these genes.…”

Section: Wcgna Analysis Reveals Melk and Fbxo5 As Highly Targetable G...mentioning

confidence: 99%

CPI203, a BET inhibitor, down-regulates a consistent set of DNA synthesis genes across a wide array of glioblastoma lines

Garrett,

Carnwath,

Albano

et al. 2024

Preprint

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IntroductionGlioblastomas utilize malignant gene expression pathways to drive growth. Many of these gene pathways are not directly accessible with molecularly targeted pharmacological agents. Chromatin-modifying compounds can alter gene expression and target glioblastoma growth pathways. In this study, we utilize a systematic screen of chromatin-modifying compounds on a panel of patient-derived glioblastoma lines to identify promising compounds and their associated gene targets.MethodsFive glioblastoma cell lines were subjected to a drug screen of 106 chromatin-modifying compounds representing 36 unique drug classes to determine the twelve most promising drug classes and the best candidate inhibitors in each class. These twelve drugs were then tested with a panel of twelve patient-derived gliomasphere lines to identify growth inhibition and corresponding gene expression patterns. Overlap analysis and weighted co-expression network analysis (WCGNA) were utilized to determine potential target genes and gene pathways.ResultsThe initial drug screen identified twelve candidate pharmacologic agents for further testing. Drug sensitivity testing indicated an overall high degree of variability between gliomasphere lines. However, CPI203 was the most consistently effective compound, and the BET inhibitor class was the most consistently effective class of compounds across the gliomasphere panel. Correspondingly, most of the compounds tested had highly variable effects on gene expression between gliomasphere lines. CPI203 stood out as the only compound to induce a consistent effect on gene expression across different gliomasphere lines, specifically down-regulation of DNA-synthesis genes. Amongst the twelve tested cell lines, high expression of CDKN2A and CDKN2B distinguished more drug sensitive from more drug resistant lines. WCGNA identified two oncogenic gene modules (FBXO5 and MELK) that were effectively downregulated by CPI203 (FBXO5) and ML228 (FBXO5 and MELK).ConclusionsThe bromodomain inhibitor CPI203 induced relatively consistent effects on gene expression and growth across a variety of glioblastoma lines, specifically down-regulating genes associated with DNA replication. We propose that clinically effective BET inhibitors have the potential to induce consistent beneficial effects across a spectrum of glioblastomas.

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MELK is a prognostic biomarker and correlated with immune infiltration in glioma

Cited by 9 publications

References 45 publications

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

KIF23 promotes cervical cancer progression via inhibiting NLRP3‐mediated pyroptosis

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer

CPI203, a BET inhibitor, down-regulates a consistent set of DNA synthesis genes across a wide array of glioblastoma lines

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