Efficacy and safety of HDACIs in the treatment of metastatic or unresectable renal cell carcinoma with a clear cell phenotype

Chen, Juan; Ren, Jia-Ju; Cai, Jie; Wang, Xiaoli

doi:10.1097/md.0000000000026788

Cited by 3 publications

(1 citation statement)

References 40 publications

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“…Furthermore, HDACi can inhibit tumors by regulating biological activities, such as cell cycle arrest, angiogenesis, immune responses, aging, and apoptosis. Treatment with HDACi has become more effective in recent years ( Singh et al, 2018 ; Chen et al, 2021 ), and has been shown to overcome tyrosine kinase inhibitor resistance induced by B-cell chronic lymphocytic leukemia-lymphoma-like 11 gene ( BIM ) deletion polymorphism in leukemia. The drug corrects the BIM precursor mRNA splicing in chronic myelogenous leukemia cell lines with BIM deletion polymorphisms by reducing the ratio of exon three- and exon 4-containing BIM transcripts, resulting in increased apoptosis ( Rauzan et al, 2017 ; Siegfried and Karni, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas

Zhang

Ding

et al. 2022

Front. Genet.

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Cutaneous T-cell lymphomas (CTCLs) are a kind of non-Hodgkin lymphoma that originates from skin, which is difficult to treat with traditional drugs. Human histone deacetylase inhibitors (HDACi) targeted therapy has become a promising treatment strategy in recent years, but some patients can develop resistance to the drug, leading to treatment failure. There are no public reports on whether alternative splicing (AS) and RNA binding proteins (RBP) affect the efficacy of targeted therapy. Using data from the Gene Expression Omnibus (GEO) database, we established a co-change network of AS events and RBP in CTCLs for the first time, and analyzed the potential regulatory effects of RBP on HDACi-related AS events. The dataset GSE132053, which contained the RNA sequence data for 17 HDACi samples, was downloaded and clean reads were aligned to the human GRCh38 genome by hierarchical indexing for spliced alignment of the transcripts, allowing four mismatches. Gene expression levels were evaluated using exons per million fragments mapped for each gene. Student’s t-tests were performed to evaluate the significance of changes in ratios for AS events, and regulated alternative splicing events (RASEs) were defined as events with p values less than 0.05. To sort the differentially expressed genes functional categories, Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were identified using the KOBAS 2.0 server. The regulatory mechanisms of the RASEs and RBPs were evaluated using Pearson’s correlation coefficient. Seven indirect events of HDACi resistance or sensitivity were identified: NIR_5151_RP11-977G19.10, NIR_4557_IRAG2, NIR_11870_SUMO1, NIR_5347_ING4, NIR_17935_DNAJC2, NIR_17974_CBLL1, and NIR_422_SLC50A1. The potential regulatory relationships between RBPs and HDACi-sensitive RASEs were also analyzed. LEPR and HNRNPAO significantly affected NIR_11870_SUMO1, suggesting a potential regulatory relationship. Additionally, CNN1 may regulate NIR_5347_ING4, CNOT3 may regulate NIR_17935_DNAJC2, and DQX1 and LENG9 may regulate NIR_422_SLC5A1. Overall, our findings establish a theoretical foundation for the precise targeted treatment of CTCLs with HDACi.

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Section: Discussionmentioning

confidence: 99%

Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas

Zhang

Ding

et al. 2022

Front. Genet.

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Targeting apoptosis in clear cell renal cell carcinoma

Kowalewski,

Borowczak,

Maniewski

et al. 2024

Biomedicine & Pharmacotherapy

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Resveratrol Affects ccRCC Cell Senescence and Macrophage Polarization by Regulating the Stability of CCNB1 by RBM15

Chen,

Liu,

et al. 2023

Epigenomics

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Aim: The present study sought to investigate the therapeutic effect of resveratrol on clear cell renal cell carcinoma. Materials & methods: Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to verify the cell proliferation. Transwell, real-time quantitative transcription PCR, western blot and β-galactosidase staining were used to verify the migration, macrophage polarization and senescence. The tumor inhibitory effect of resveratrol on clear cell renal cell carcinoma was verified in vivo. Results: This study confirmed that resveratrol could affect the stability of CCNB1 mRNA mediated by RBM15 and inhibit the cancer process by inhibiting the expression of EP300/CBP from the perspective of cell senescence. Conclusion: Resveratrol is able to treat clear cell renal cell carcinoma through RBM15-induced cell senescence.

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Efficacy and safety of HDACIs in the treatment of metastatic or unresectable renal cell carcinoma with a clear cell phenotype

Abstract: Supplemental Digital Content is available in the text

Cited by 3 publications

References 40 publications

Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas

Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas

Targeting apoptosis in clear cell renal cell carcinoma

Resveratrol Affects ccRCC Cell Senescence and Macrophage Polarization by Regulating the Stability of CCNB1 by RBM15

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