Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion

Miao, Faan; Chu, Kun; Chen, Hairong; Zhang, Meng; Shi, Pei-Cong; Bai, Jing; You, Yongping

doi:10.1007/s10637-019-00748-w

Cited by 46 publications

(41 citation statements)

References 26 publications

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“…DKC1 downregulation can also inhibit the growth of glioma cells by altering the expression of cell cycle-related molecules, causing cells to arrest in G1 phase. In vitro experiments also confirmed that glioma cells with DKC1 knockout showed low activity (Miao et al, 2019). DKC1 is highly expressed in clear cell renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 61%

Bioinformatics Analysis Reveals Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma

2020

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Background: Tumor stem cells play important roles in the survival, proliferation, metastasis and recurrence of tumors. We aimed to identify new prognostic biomarkers for lung squamous cell carcinoma (LUSC) based on the cancer stem cell theory. Methods: RNA-seq data and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify significant modules and hub genes, and prognostic signatures were constructed with the prognostic hub genes. Results: LUSC patients in the TCGA database have higher mRNA expression-based stemness index (mRNAsi) in tumor tissue than in adjacent normal tissue. In addition, some clinical features and outcomes were highly correlated with the mRNAsi. WGCNA revealed that the pink and yellow modules were the most significant modules related to the mRNAsi; the top 10 hub genes in the pink module were enriched mostly in epidermal development, the secretory granule membrane, receptor regulator activity and the cytokine-cytokine receptor interaction. The protein-protein interaction (PPI) network revealed that the top 10 hub genes were significantly correlated with each other at the transcriptional level. In addition, the top 10 hub genes were all highly expressed in LUSC, and some were differentially expressed in different TNM stages. Regarding the survival analysis, the nomogram of a prognostic signature with three hub genes showed high predictive value. Conclusion: mRNAsi-related hub genes could be a potential biomarker of LUSC.

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Section: Discussionmentioning

confidence: 61%

Bioinformatics Analysis Reveals Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma

2020

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“…One of the ψ writers, DKC1, is significantly upregulated in glioma and correlates with the WHO stages of tumors. DKC1 promotes glioma cell growth by stimulating cell cycle progression and activates migration via upregulating N-cadherin, hypoxia inducible factor 1 subunit α (HIF1A), and MMP-2 expression [91]. PUS7L, as a target of HIF1A, is also downregulated after c-Myc inhibition in GBM under hypoxia [138].…”

Section: Rna ψ Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

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Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2′O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.

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“…NSUN2 as a tRNA methyltransferase, is significantly related to cancer progression in several tumors, such as esophageal squamous cell carcinoma (Li et al, 2018), breast cancer (Yi et al, 2017), and ovarian cancer (Yang et al, 2017). DKC1 is deregulated in glioma and knockdown of DKC1 restrain cancer cell proliferation, invasion and migration (Miao et al, 2019). By executing module analysis of PPI network, we found that LUAD is associated with RNA metabolic process, ribosome biogenesis, cellular amide metabolic process, peptide biosynthetic process, and translational elongation.…”

Section: Discussionmentioning

confidence: 91%

Integrated analysis of the roles and prognostic value of RNA binding proteins in lung adenocarcinoma

Gao

et al. 2020

PeerJ

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Lung cancer is the top cause of carcinoma-associated deaths worldwide. RNA binding proteins (RBPs) dysregulation has been reported in various malignant tumors, and that dysregulation is closely associated with tumorigenesis and tumor progression. However, little is known about the roles of RBPs in lung adenocarcinoma (LUAD). In this study, we downloaded the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. We then performed an integrative analysis to explore the expression and prognostic significance of these RBPs. A total of 164 differently expressed RBPs were identified, including 40 down-regulated and 124 up-regulated RBPs. Pathway and Gene ontology (GO) analysis indicated that the differently expressed RBPs were mainly related to RNA processing, RNA metabolic process, RNA degradation, RNA transport, splicing, localization, regulation of translation, RNA binding, TGF-beta signaling pathway, mRNA surveillance pathway, and aminoacyl-tRNA biosynthesis. Survival analysis revealed that the high expression of BOP1 or GNL3 or WDR12 or DCAF13 or IGF2BP3 or IGF2BP1 were associated with poor overall survival (OS). Conversely, overexpression of KHDRBS2/SMAD predicted high OS in these patients. ROC curve analysis showed that the eight hub genes with a better diagnostic accuracy to distinguish lung adenocarcinoma. The results provided novel insights into the pathogenesis of LUAD and the development of treatment targets and prognostic molecular markers.

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Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion

Cited by 46 publications

References 26 publications

Bioinformatics Analysis Reveals Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma

Bioinformatics Analysis Reveals Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma

The Emerging Roles of RNA Modifications in Glioblastoma

Integrated analysis of the roles and prognostic value of RNA binding proteins in lung adenocarcinoma

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