MZT2A promotes NSCLC viability and invasion by increasing Akt phosphorylation via the MOZART2 domain

Wang, Huanxi; Jiang, Xizi; Yu, Changhong; Ren, Hongjiu; Hu, Yujiao; Zhang, Yao; Su, Hongbo; Zou, Zifang; Wang, Qiongzi; Liu, Zongang; Zhang, Jiameng; Qiu, Xueshan

doi:10.1111/cas.14900

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…Recently, Wang et al reported that MZT2A mRNA and protein levels were overexpressed in NSCLC and associated with poor NSCLC prognosis. Upregulation of MZT2A could promote NSCLC cell viability and invasion by overexpressing LGALS3BP via the MTZ2A MOZART2 domain and Akt phosphorylation (34). However, mechanisms on how MZT2A influences tumor prognosis and CD8+ T-cell infiltration should be further explored.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

Liang

Liu

et al. 2021

Front. Oncol.

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BackgroundCD8+ T cells are one of the central effector cells in the immune microenvironment. CD8+ T cells play a vital role in the development and progression of lung adenocarcinoma (LUAD). This study aimed to explore the key genes related to CD8+ T-cell infiltration in LUAD and to develop a novel prognosis model based on these genes.MethodsWith the use of the LUAD dataset from The Cancer Genome Atlas (TCGA), the differentially expressed genes (DEGs) were analyzed, and a co-expression network was constructed by weighted gene co-expression network analysis (WGCNA). Combined with the CIBERSORT algorithm, the gene module in WGCNA, which was the most significantly correlated with CD8+ T cells, was selected for the subsequent analyses. Key genes were then identified by co-expression network analysis, protein–protein interactions network analysis, and least absolute shrinkage and selection operator (Lasso)-penalized Cox regression analysis. A risk assessment model was built based on these key genes and then validated by the dataset from the Gene Expression Omnibus (GEO) database and multiple fluorescence in situ hybridization experiments of a tissue microarray.ResultsFive key genes (MZT2A, ALG3, ATIC, GPI, and GAPDH) related to prognosis and CD8+ T-cell infiltration were identified, and a risk assessment model was established based on them. We found that the risk score could well predict the prognosis of LUAD, and the risk score was negatively related to CD8+ T-cell infiltration and correlated with the advanced tumor stage. The results of the GEO database and tissue microarray were consistent with those of TCGA. Furthermore, the risk score was higher significantly in tumor tissues than in adjacent lung tissues and was correlated with the advanced tumor stage.ConclusionsThis study may provide a novel risk assessment model for prognosis prediction and a new perspective to explore the mechanism of tumor immune microenvironment related to CD8+ T-cell infiltration in LUAD.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

Liang

Liu

et al. 2021

Front. Oncol.

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“…MZT2A overexpression promoted NSCLC cell viability and invasion. Moreover, MZT2A indirectly induced Akt phosphorylation to promote NSCLC proliferation and invasion [ 116 ].…”

Section: Dysregulation Of the Other γ-Turc Building Componentsmentioning

confidence: 99%

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Dráberová

2021

Cancers

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In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. γ-Tubulin, which forms multiprotein complexes, is essential for nucleation. The γ-tubulin ring complex (γ-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of γ-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of γ-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of γ-TuRC protein dysregulation on cancer cell behavior and new compounds targeting γ-tubulin. Drugs inhibiting γ-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.

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“…The lack of MZT2A will weaken the nucleation activity of MT and slow down the rate of cell proliferation, and participate in the regulation of tumor cell cycle and cell proliferation. Wang H et al [ 15 ] found that high expression of MZT2A can promote the invasion of NSCLC tumor cells, and its overexpression level is associated with NSCLC progression and poor prognosis. However, there are few reports on the expression of MZT2A in different tumors and its relationship with disease prognosis and tumor development.…”

Section: Discussionmentioning

confidence: 99%

“…Exploring the expression level of MZT2A in human cancers is critical for developing new therapeutic strategies. Wang H et al [ 15 ] found that MZT2A mRNA and MZT2A protein were highly expressed in non-small cell lung cancer ( NSCLC ). The expression of MZT2A protein in NSCLC cells was signi cantly higher than that in normal bronchial tissues, suggesting that MZT2A expression may promote the viability and invasion of NSCLC cells.…”

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Correlation of MZT2A Expression with Immunity and Prognosis in Pan-Cancer Analysis

zhan

Wang

Yan

et al. 2022

Preprint

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Purpose Mitotic spindle tissue protein 2A(MZT2A) has the properties of the core subunit of the γ-tubulin ring complex ( γ-TuRC ) and is involved in mediating the formation of bipolar spindles in mitosis. The lack of MZT2A will weaken the nucleation activity of microtubule ( MT ) and slow down the rate of cell proliferation. Although there is evidence that the expression of MZT2A plays a crucial role in the development of some tumors, there is still no research on MZT2A in pan-cancer. Therefore, we aim to explore the prognostic value of MZT2A in a variety of cancer types and to study its potential immune function. Methods This study was conducted with datasets from The Cancer Genome Atlas, the Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression and the Human Protein Atlas. Bioinformatic methods were used to analyse the correlation between MZT2A expression levels in different tumours and survival prognosis, immune infiltration, immune checkpoint genes, immune regulatory genes, tumour mutational load (TMB), tumour neoantigens, homologous recombination defects (HRD), microsatellite instability (MSI), tumour stemness score and enrichment analysis regarding MZT2A. Results MZT2A was highly expressed in most tumours and was positively or negatively correlated with the prognosis of patients with different tumours. MZT2A was also found to be negatively correlated with the immune microenvironment, immune infiltrating cells, and immune-related genes in most tumours, and was strongly correlated with TMB in 11 tumours, MSI in 10 tumours, tumour neoantigens in 5 tumours, and HRD in 12 tumours, and MZT2A expression was significantly correlated with RNA stemness score (RNAss) in 24 tumours and DNA stemness score (DNAss) in 12 tumours. The results suggest that MZT2A can be used as a target or predictor of tumour therapy. the immunosuppressive effect of MZT2A in TME suggests that anti-MZT2A immunotherapy may be a new direction in cancer treatment. Conclusion MZT2A is involved in tumour development and can be used as a prognostic marker for a variety of tumours and as a target or predictor for tumour immunotherapy.

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MZT2A promotes NSCLC viability and invasion by increasing Akt phosphorylation via the MOZART2 domain

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 9 publications

References 42 publications

Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Correlation of MZT2A Expression with Immunity and Prognosis in Pan-Cancer Analysis

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