Cuproptosis-related gene CDKN2A as a molecular target for IPF diagnosis and therapeutics

Xu, Bin; Yang, Kaiyong; Han, Xin; Hou, Jiwei

doi:10.1007/s00011-023-01739-7

Cited by 6 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, the mechanism underlying the ability of MUC20 to induce cuproptosis in PI-resistant MM cells was investigated. CDKN2A has been reported to suppresses cuproptosis [ 11 , 14 ]. In this study, qRT-PCR showed that CDKN2A mRNA levels in PI-resistant KAS-6/1 and U266 cells were consistent with those in PI-sensitive KAS-6/1 and U266 cells and that MUC20 overexpression had no effect on CDKN2A mRNA levels in PI-sensitive KAS-6/1 and U266 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis

Wang,

Shi,

Shi

et al. 2024

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. Methods We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay. Results This study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM. Conclusion Our findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Cyclin-dependent kinase inhibitor 2 A (CDKN2A), a cuproptosis-related gene, suppresses cuproptosis of M2 macrophages [ 11 , 14 ]. Bioinformatic studies have suggested that CDKN2A may be associated with drug resistance in MM [ 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis

Wang,

Shi,

Shi

et al. 2024

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

Characterization of cuproptosis signature in clear cell renal cell carcinoma by single cell and spatial transcriptome analysis

Zou,

Liu,

Wang

et al. 2024

Discov Onc

View full text Add to dashboard Cite

Cuproptosis is a novel type to regulate cell death with copper-dependent manner, and has been reported to involve in the occurrence and development of various malignant tumors. However, the association between cuproptosis and the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remained unclear. To address this question, we integrated the single cell RNA sequencing (scRNA-seq) datasets of ccRCC across different stages, systematically examined the distinctive expression patterns of cuproptosis-related genes (CRGs) within the TME of ccRCC, and explored the crucial signatures using the spatial transcriptome sequencing (ST-seq) dataset. The cuproptosis activities reduced in cancer tissues along with the ccRCC development, and recovered after therapy. We identified HILPDA+ ccRCC1 subtype, characterized with hypoxia, as cuproptosis susceptible cells associated with a better prognosis. The main co-expression modules of HILPDA+ ccRCC1 subtype highlighted the role in anion transport, response to oxygen species and PD-L1-PD-1 pathway. Furthermore, the immunosuppressive cells might interact with HILPDA+ ccRCC1 subtype via HAVCR2-LGALS9, C3-C3AR1, HLA-A-CD8B and HLA-C-CD8A axises to shape the cuproptosis-related TME landscape. In summary, we anticipate that this study will offer valuable insights and potential strategies of cuproptosis for therapy of ccRCC. Graphical Abstract

show abstract

The cuproptosis-related gene glutaminase promotes alveolar macrophage copper ion accumulation in chronic obstructive pulmonary disease

Han,

Zhu,

et al. 2024

International Immunopharmacology

View full text Add to dashboard Cite

Cuproptosis-related gene CDKN2A as a molecular target for IPF diagnosis and therapeutics

Cited by 6 publications

References 49 publications

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis

Characterization of cuproptosis signature in clear cell renal cell carcinoma by single cell and spatial transcriptome analysis

The cuproptosis-related gene glutaminase promotes alveolar macrophage copper ion accumulation in chronic obstructive pulmonary disease

Contact Info

Product

Resources

About