Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation

Gong, Lian; Hu, Yi; He, Dong; Zhu, Yuxing; Xiang, Lei; Xiao, Mengqing; Bao, Ying; Liu, Xiaoming; Zeng, Qinghai; Liu, Jianye; Zhou, Ming; Zhou, Yanhong; Cheng, Ying; Zhang, Yeyu; Deng, Liping; Zhu, Rongrong; Lan, Hua; Cao, Ke

doi:10.1186/s12935-020-01263-2

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…27 CHAF1B was of particular interest in this study, considering its oncogenic property in NSCLC. 28,29 For the first time, we confirmed that CHAF1B was directly targeted by miR-3619-5p. Moreover, we highlighted the role of circ_0026134 as a posttranscriptional regulator of CHAF1B expression.…”

Section: Discussionsupporting

confidence: 54%

Circ_0026134 promotes NSCLC progression by the miR‐3619‐5p/CHAF1B axis

Tan

et al. 2022

Thoracic Cancer

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Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have been implicated in the pathogenesis of NSCLC. In this study, we explored the molecular determinants underlying the oncogenic property of circ_0026134 in NSCLC. Methods: The levels of circ_0026134, miR-3619-5p and chromatin assembly factor 1 subunit B axis (CHAF1B) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell colony formation, migration, invasion and apoptosis were detected by colony formation, Transwell, and flow cytometry assays, respectively. Direct relationships among circ_0026134, miR-3619-5p and CHAF1B were verified by dual-luciferase reporter assays. Results: Our results showed that circ_0026134 was highly expressed in NSCLC tissues and cells. Reduced circ_0026134 expression or miR-3619-5p overexpression inhibited NSCLC cell colony formation, migration, invasion, glycolysis and promoted cell apoptosis in vitro. Moreover, circ_0026134 directly targeted miR-3619-5p, and circ_0026134 regulated CHAF1B expression through miR-3619-5p. CHAF1B was a downstream effector of circ_0026134 in affecting NSCLC cell functional behaviors in vitro. Additionally, circ_0026134 silencing weakened tumor growth in vivo. Conclusions: Our study identified a novel regulatory mechanism, the circ_0026134/ miR-3619-5p/CHAF1B axis, for the oncogenic role of circ_0026134 in NSCLC, highlighting circ_00261345 inhibition as a potential therapeutic method against NSCLC.

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Section: Discussionsupporting

confidence: 54%

Circ_0026134 promotes NSCLC progression by the miR‐3619‐5p/CHAF1B axis

Tan

et al. 2022

Thoracic Cancer

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“…Bortezomib exhibits remarkable potential in modulating the expression of apoptosis‐related proteins and can be employed in combination with cytotoxic drugs for treating lung cancer 36 . Cisplatin stands as the most commonly utilized platinum‐based drug, forming the foundation of first‐line chemotherapy for LUAD 37,38 . In the context of NSCLC treatment, both docetaxel and paclitaxel can be combined with platinum to form a classical chemotherapy regimen, demonstrating favourable efficacy 39 .…”

Section: Discussionmentioning

confidence: 99%

“…36 Cisplatin stands as the most commonly utilized platinumbased drug, forming the foundation of first-line chemotherapy for LUAD. 37,38 In the context of NSCLC treatment, both docetaxel and paclitaxel can be combined with platinum to form a classical chemotherapy regimen, demonstrating favourable efficacy. 39 Erlotinib is indicated for the treatment and maintenance of second-and thirdline advanced NSCLC, while entinostat, in combination with erlotinib, enhances the single-agent efficacy of erlotinib.…”

Section: Cd8mentioning

confidence: 99%

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis

Li,

et al. 2024

J Cellular Molecular Medi

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Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan–Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real‐time quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late‐stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

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“…Low glucose and high fatty acid levels result in a decrease in NCoR expression (Figure 1a) [138]. Furthermore, hepatocarcinoma and breast cancer cells exhibit lower NCoR levels [145], and lung adenocarcinoma cells exhibit degradation of NCoR2 by ubiquitination [146] (Figure 1a). On the contrary, insulin and high glucose upregulate NCoR expression [137].…”

Section: Nuclear Receptor Corepressors (Ncors)mentioning

confidence: 99%

Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

Rigalli

Theile

Nilles

et al. 2021

Cells

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The pregnane X receptor (PXR, NR1I2) is a nuclear receptor which exerts its regulatory function by heterodimerization with the retinoid-X-receptor α (RXRα, NR2B1) and binding to the promoter and enhancer regions of diverse target genes. PXR is involved in the regulation of drug metabolism and excretion, metabolic and immunological functions and cancer pathogenesis. PXR activity is strongly regulated by the association with coactivator and corepressor proteins. Coactivator proteins exhibit histone acetyltransferase or histone methyltransferase activity or associate with proteins having one of these activities, thus promoting chromatin decondensation and activation of the gene expression. On the contrary, corepressor proteins promote histone deacetylation and therefore favor chromatin condensation and repression of the gene expression. Several studies pointed to clear cell- and ligand-specific differences in the activation of PXR. In this article, we will review the critical role of coactivator and corepressor proteins as molecular determinants of the specificity of PXR-mediated effects. As already known for other nuclear receptors, understanding the complex mechanism of PXR activation in each cell type and under particular physiological and pathophysiological conditions may lead to the development of selective modulators with therapeutic potential.

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Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation

Cited by 8 publications

References 35 publications

Circ_0026134 promotes NSCLC progression by the miR‐3619‐5p/CHAF1B axis

Circ_0026134 promotes NSCLC progression by the miR‐3619‐5p/CHAF1B axis

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis

Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning

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