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pmid:38075690

Histone ubiquitination-related gene CUL4B promotes lung adenocarcinoma progression and cisplatin resistance.

Yanjun Yin · Lifeng Zhang · Yinchuan Zeng · Diang Chen · Haien Guan · Guoping Ran · Kangming Du

Frontiers in genetics · 2023 doi:10.3389/fgene.2023.1242137

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Histone ubiquitination-related gene CUL4B promotes lung adenocarcinoma progression and cisplatin resistance.
doi
10.3389/fgene.2023.1242137
pmid
38075690
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[0]
Yanjun Yin
[1]
Lifeng Zhang
[2]
Yinchuan Zeng
[3]
Diang Chen
[4]
Haien Guan
[5]
Guoping Ran
[6]
Kangming Du
journal
Frontiers in genetics
year
2023
abstract
Background: The role of the histone ubiquitination-related gene in the cisplatin resistance of lung adenocarcinoma (LUAD) remains an intricate subject. Methods: We accessed transcriptome data of both wild type and cisplatin-resistant cells from the GSE108214 dataset, and garnered transcriptome and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) database. Utilizing the R software, we analyzed these public datasets in depth. Real-time Quantitative PCR (qPCR) was used to detect the RNA level of CUL4B. Effect of CUL4B on cell proliferation was evaluated using CCK8 and colony formation assay. Effect of CUL4B on cell invasion was evaluated using transwell assay. Cisplatin sensitivity was evaluated by calculating IC50. Results: Our analysis shed light on the significance of the histone ubiquitination-related gene, CUL4B, in relation to cisplatin resistance and the overall survival rates of LUAD patients. Notably, CUL4B was found to be overexpressed in both lung cancer tissues and cells. Meanwhile, in vitro experiments indicated can CUL4B significantly promote the proliferation, invasion and migration of lung cancer cells. Furthermore, suppressing CUL4B expression led to a noticeable reduction in the IC50 value of cisplatin in lung cancer cells. A deep dive into biological enrichment analysis revealed that among patients exhibiting high CUL4B expression, there was a pronounced activation of the G2M checkpoint and the PI3K/AKT/mTOR signaling pathways. Immune microenvironment analysis has revealed that patients with elevated CUL4B expression may exhibit increased infiltration of M2 macrophages, coupled with a reduced infiltration of CD8+ T cells and activated NK cells. Notably, we observed higher CUL4B expression among those who responded positively to immunotherapy. Conclusion: These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target.
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Limma package was utilized to conduct the differentially expressed genes (DEGs) analysis (threshold = |logFC| > 1 and adj P.value <0.05) (Ritchie et al., 2015). Kaplan-Meier survival curves were employed to analyze prognosis disparities between various groups (Rich et al., 2010).
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Limma package was utilized to conduct the differentially expressed genes (DEGs) analysis (threshold = |logFC| > 1 and adj P.value <0.05) (Ritchie et al., 2015). Kaplan-Meier survival curves were employed to analyze prognosis disparities between various groups (Rich et al., 2010).
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These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target.
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These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target.
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Limma package was utilized to conduct the differentially expressed genes (DEGs) analysis (threshold = |logFC| > 1 and adj P.value <0.05) (Ritchie et al., 2015). Kaplan-Meier survival curves were employed to analyze prognosis disparities between various groups (Rich et al., 2010).
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Methods: We accessed transcriptome data of both wild type and cisplatin-resistant cells from the GSE108214 dataset, and garnered transcriptome and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) database. Utilizing the R software, we analyzed these public datasets in depth. Real-time Quantitative PCR (qPCR) was used to detect the RNA level of CUL4B. Effect of CUL4B on cell proliferation was evaluated using CCK8 and colony formation assay. Effect of CUL4B on cell invasion was evaluated using transwell assay. Cisplatin sensitivity was evaluated by calculating IC50. Results: Our analysis shed light on the significance of the histone ubiquitination-related gene, CUL4B, in relation to cisplatin resistance and the overall survival rates of LUAD patients. Notably, CUL4B was found to be overexpressed in both lung cancer tissues and cells. Meanwhile, in vitro experiments indicated can CUL4B significantly promote the proliferation, invasion and migration of lung cancer cells. Furthermore, suppressing CUL4B expression led to a noticeable reduction in the IC50 value of cisplatin in lung cancer cells. A deep dive into biological enrichment analysis revealed that among patients exhibiting high CUL4B expression, there was a pronounced activation of the G2M checkpoint and the PI3K/AKT/mTOR signaling pathways. Immune microenvironment analysis has revealed that patients with elevated CUL4B expression may exhibit increased infiltration of M2 macrophages, coupled with a reduced infiltration of CD8+ T cells and activated NK cells. Notably, we observed higher CUL4B expression among those who responded positively to immunotherapy. 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