Gemin6 promotes c‐Myc stabilisation and non‐small cell lung cancer progression via accelerating AURKB mRNA maturation

Lin, Jie; Liu, Baiyang; Zhang, Yong; Li, LV; Cheng, Dating; Zhang, Wenhui; Shi, Yulin; Jiang, Xiulin; Tang, Lin; Yuan, Yixiao; Zhai, Hongbin; Shen, Qingwu; Xiong, Qian; Jin, Zhixian; Chen, Yongbin; Yang, Cuiping

doi:10.1002/ctm2.811

Cited by 3 publications

(6 citation statements)

References 14 publications

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“…This study's findings from the analysis of Cox regression and Kaplan–Meier demonstrate a robust correlation between increased AURKB expression and reduced OS and DSS among individuals diagnosed with ACC, KIRP, BRCA, CHOL, KIRC, MESO, LGG, LIHC, LUAD, PAAD, THYM, SARC, SKCM and UVM. Previous studies have highlighted that the expression of AURKB is connected to the prognosis of malignancies such as NSCLC 12 and prostate cancer. 13 For instance, Lin's research revealed a significant upregulation of AURKB in NSCLC tissues, which was correlated with decreased OS and PFS.…”

Section: Discussionmentioning

confidence: 99%

“… 10 Moreover, the AURKB gene has been validated as an actively involved oncogene in cancer and displays a significant inverse correlation with cancer prognosis. 11 Specific roles of AURKB in certain cancer types, including non‐small cell lung cancer (NSCLC) 12 and prostate cancer, 13 have been explored in prior studies. Nevertheless, a more exhaustive examination of the molecular mechanisms underlying AURKB's role is essential for the development of innovative pathways in cancer diagnosis and therapeutic research.…”

Section: Introductionmentioning

confidence: 99%

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An analysis of AURKB's prognostic and immunological roles across various cancers

Li,

Cheng,

Zhang

2024

J Cellular Molecular Medi

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Aurora kinase B (AURKB), an essential regulator in the process of mitosis, has been revealed through various studies to have a significant role in cancer development and progression. However, the specific mechanisms remain poorly understood. This study, therefore, seeks to elucidate the multifaceted role of AURKB in diverse cancer types. This study utilized bioinformatics techniques to examine the transcript, protein, promoter methylation and mutation levels of AURKB. The study further analysed associations between AURKB and factors such as prognosis, pathological stage, biological function, immune infiltration, tumour mutational burden (TMB) and microsatellite instability (MSI). In addition, immunohistochemical staining data of 50 cases of renal clear cell carcinoma and its adjacent normal tissues were collected to verify the difference in protein expression of AURKB in the two tissues. The results show that AURKB is highly expressed in most cancers, and the protein level of AURKB and the methylation level of its promoter vary among cancer types. Survival analysis showed that AURKB was associated with overall survival in 12 cancer types and progression‐free survival in 11 cancer types. Elevated levels of AURKB were detected in the advanced stages of 10 different cancers. AURKB has a potential impact on cancer progression through its effects on cell cycle regulation as well as inflammatory and immune‐related pathways. We observed a strong association between AURKB and immune cell infiltration, immunomodulatory factors, TMB and MSI. Importantly, we confirmed that the AURKB protein is highly expressed in kidney renal clear cell carcinoma (KIRC). Our study reveals that AURKB may be a potential biomarker for pan‐cancer and KIRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An analysis of AURKB's prognostic and immunological roles across various cancers

Li,

Cheng,

Zhang

2024

J Cellular Molecular Medi

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“…Gem nuclear organelle-associated protein 6 (GEMIN6) is a component of the survival of the motor neuron (SMN) complex. GEMIN6 is upregulated in LUSC tumor tissues and high expression of GEMIN6 is correlated with poor clinical outcomes [ 47 ]. We consistently found that the MGST3 and GEMIN6 gene expression is associated with poor survival in LUSC patients.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma

et al. 2023

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Lung squamous cell carcinoma (LUSC) is associated with a worse prognosis than other histological subtypes of non-small cell lung cancer. Due to the vital role of CD8+ T cells in anti-tumor immunity, the characterization of CD8+ T cell infiltration-related (CTLIR) gene signature in LUSC is worthy of in-depth exploration. In our study, tumor tissues of LUSC patients from Renmin Hospital of Wuhan University were stained by multiplex immunohistochemistry to evaluate the density of infiltrated CD8+ T cells and explore the correlation with immunotherapy response. We found that the proportion of LUSC patients who responded to immunotherapy was higher in the high density of CD8+ T cell infiltration group than in the low density of CD8+ T cell infiltration group. Subsequently, we collected bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) database. The abundance of infiltrating immune cells in LUSC patients was analyzed by using CIBERSORT algorithm, and weighted correlation network analysis was performed to identify the co-expressed gene modules related to CD8+ T cells. We then developed a prognostic gene signature based on CD8+ T cell co-expressed genes and calculated the CTLIR risk score, which stratified LUSC patients into high-risk and low-risk groups. With univariate and multivariate analyses, the gene signature was identified as an independent prognostic factor in LUSC patients. The overall survival of LUSC patients in the high-risk group was significantly shorter than that of the low-risk group in the TCGA cohort, which was validated in Gene Expression Omnibus datasets. We analyzed immune cell infiltration in the tumor microenviroment and found fewer CD8+ T cells and more regulatory T cell infiltration in the high-risk group, which is characterized as an immunosuppressive phenotype. Furthermore, the LUSC patients in the high-risk group were predicted to have a better response to immunotherapy than those in the low-risk group when treated with PD-1 and CTLA4 inhibitors. In conclusion, we performed a comprehensive molecular analysis of the CTLIR gene signature in LUSC and constructed a risk model for LUSC patients to predict prognosis and immunotherapy response.

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“…Growing evidence suggests that the GEMINS protein family works as an oncogene and is associated with cancer progression [ 11 , 12 , 20 ]. This study demonstrated that GEMIN6 was remarkably expressed in the advanced T stage, the advanced N stage, and the advanced pathologic stage LUAD, suggesting that GEMIN6 was potentially related to high malignant biological behavior of LUAD.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, studies focused on GEMIN6 are rare, especially on cancer research. In nonsmall cell lung cancer, GEMIN6 was found to accelerate AURKB maturation and c-Myc stabilisation to promote the cancer progression [ 12 ], while the clear role of GEMIN6 in LUAD remains to be addressed.…”

Section: Introductionmentioning

confidence: 99%

GEMIN6 Overexpression Correlates with the Low Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma

Peng

Wang

Cai

et al. 2022

Journal of Oncology

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Background. Gem nuclear organelle-associated protein 6 (GEMIN6) is a component of the GEMINS protein family involved in the survival of motor neuron (SMN) complex. SMN interfered with snRNP assembly and mRNA processing resulting in tumorigenesis. We performed this study to explore the association between GEMIN6 and lung adenocarcinoma (LUAD). Methods. We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptomic expression data of LUAD patients and analyze the difference in GEMIN6 expression between normal and tumor tissues of LUAD. qRT-PCR analysis was also performed to detect the expression of GEMIN6 in normal and LUAD cells. The expression of GEMIN6 on the LUAD patient survival outcome was estimated by the Kaplan–Meier curves and Cox analyses. In addition, the Metascape online tool and single-sample GSEA were employed to find out the underlying biological mechanisms of GEMIN6. Furthermore, the correlations of GEMIN6 expression with immune cell infiltration in LUAD were analyzed by ssGSEA and Spearman correlation analysis. Results. Compared with the normal tissues and cells, the expression of GEMIN6 was significantly higher in LUAD tissues and cells; the high expression GEMIN6 was also found in the advanced pathologic stage and advanced N and T stages of LUAD. GEMIN6 high expression was significantly associated with inferior overall survival. The heat map revealed the top 20 coexpressed genes with GEMIN6, including SF3B6, CPSF3, and PSMB3. Functional enrichment analysis demonstrated that enrichment genes are associated with the cell cycle, mRNA processing, and energy metabolism. Additionally, GEMIN6 was negatively related to the immune cell infiltration in LUAD. Conclusions. This study demonstrated that GEMIN6 was involved in the tumorigenesis and progression of LUAD. GEMIN6 could be an important molecular marker of poor prognosis and a therapeutic target of LUAD.

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Gemin6 promotes c‐Myc stabilisation and non‐small cell lung cancer progression via accelerating AURKB mRNA maturation

Cited by 3 publications

References 14 publications

An analysis of AURKB's prognostic and immunological roles across various cancers

An analysis of AURKB's prognostic and immunological roles across various cancers

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma

GEMIN6 Overexpression Correlates with the Low Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma

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