HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cells

Lee, Bok‐Soon; Kim, Yeon Soo; Kim, Haeng-Jun; Kim, Daeho; Won, Ho-Ryun; Kim, Yong‐Sung; Kim, Chul‐Ho

doi:10.1038/s41598-018-31039-8

Cited by 13 publications

(14 citation statements)

References 31 publications

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“…The human HDAC4 gene, located on chromosome 2q37.3, has been found to be involved in initiation and development of various cancers, and functions as an oncogene in many cancers [32][33][34][35][36]. A previous study confirmed HDAC4 as a target of miR-29b-3p in MM cells [25].…”

Section: Discussionmentioning

confidence: 94%

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

2019

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Background: Long non-coding RNA taurine up-regulated gene 1 (TUG1) was reportedly involved in initiation and development of several cancers. However, its function and molecular mechanisms in multiple myeloma (MM) are still unclear. The present study aimed to determine the expression status, biological function, and potential mechanisms of TUG1 in the progression of MM. Materials and methods: The expression levels of TUG1 were examined in MM samples and cell lines by real-time quantitative PCR. The effects of TUG1 on MM cells proliferation and apoptosis were assessed using Cell Counting Kit-8 assay and flow cytometry respectively. MiRNAs-targeted sites in TUG1 were screened by Starbase2.0 and were identified by RNA immunoprecipitation assay combined with luciferase reporter assay. Results: The expression levels of TUG1 were markedly increased in MM samples and cell lines. Knockdown of TUG1 significantly suppressed the proliferation, induced cell cycle arrest at G1/G0 phase, and promoted apoptosis of MM cells. In exploring the regulatory mechanism, miR-29b-3p was confirmed to be a direct target of TUG1, and repression of miR-29b-3p could partially rescue the effect TUG1 knockdown on MM cell proliferation, cycle, and apoptosis. In addition, TUG1 positively modulated histone deacetylases 4 (HDAC4, a target of miR-29b-3p) expression through sponging of miR-29b-3p in MM cells. Conclusion: These findings suggested that TUG1 exerted an oncogenic role in MM by acting as a competing endogenous RNA of miR-29b-3p, and implied the potential application of TUG1 in treatment for MM.

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Section: Discussionmentioning

confidence: 94%

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

2019

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“…HDACs also deacetylate non-histone cellular substrates and influence a variety of biological processes that govern cancer initiation and progression [ 42 ]. HDAC4 is upregulated in head and neck cancer tissues [ 43 ]. HDAC4 is targeted by HDAC inhibitors ( Figure 2 b).…”

Section: Discussionmentioning

confidence: 99%

An ErbB Lineage Co-Regulon Harbors Potentially Co-Druggable Targets for Multimodal Precision Therapy in Head and Neck Squamous Cell Carcinoma

Bredel

Kim

Bonner

2022

IJMS

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The ErbB lineage of oncogenic receptor tyrosine kinases is frequently overexpressed in head and neck squamous cell carcinomas. A common co-regulon triggered by the ErbB proteins; involving shared signaling circuitries; may harbor co-druggable targets or response biomarkers for potential future multimodal precision therapy in ErbB-driven head and neck squamous cell carcinoma. We here present a cohort-based; genome-wide analysis of 488 head and neck squamous cell carcinomas curated as part of The Cancer Genome Atlas Project to characterize genes that are significantly positively co-regulated with the four ErbB proteins and those that are shared among all ErbBs denoting a common ErbB co-regulon. Significant positive gene correlations involved hundreds of genes that were co-expressed with the four ErbB family members (q < 0.05). A common; overlapping co-regulon consisted of a core set of 268 genes that were uniformly co-regulated with all four ErbB genes and highly enriched for functions in chromatin organization and histone modifications. This high-priority set of genes contained ten putative antineoplastic drug-gene interactions. The nature and directionality of these ten drug-gene associations was an inhibiting interaction for seven (PIK3CB; PIK3C2B; HDAC4; FRK; PRKCE; EPHA4; and DYRK1A) of them in which the drug decreases the biological activity or expression of the gene target. For three (CHD4; ARID1A; and PBRM1) of the associations; the directionality of the interaction was such that the gene predicted sensitivit y to the drug suggesting utility as potential response biomarkers. Drug-gene interactions that predicted the gene product to be reduced by the drug included a variety of potential targeted molecular agent classes. This unbiased genome-wide analysis identified a target-rich environment for multimodal therapeutic approaches in tumors that are putatively ErbB-driven. The results of this study require preclinical validation before ultimately devising lines of combinatorial treatment strategies for ErbB-dependent head and neck squamous cell carcinomas that incorporate these findings.

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“…The survival and growth of multiple myeloma is regulated by the HDAC4-RelB-p52 complex, and the disruption of the latter blocks the growth of these cells [ 46 ]. Moreover, HDAC4 degradation by certain chemotherapeutic agents results in the apoptosis of head-and-neck cancer cells that are resistant to TRAIL, while miR-22-driven HDAC4 repression helped to resensitize fulvestrant-resistant breast cancer cells [ 47 , 48 ]. Likewise, eptoposide resistance in human A549 lung cancer cells was conferred by STAT1-HDAC4 upregulation, and HDAC4 inhibition has been reported to induce apoptosis in non-small cell lung cancer PC-9 cells [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification of methylated CpG sites in nongenital cutaneous warts

et al. 2020

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Background: Low-risk HPV infection has not been the subject of epigenetic investigation. The present study was carried out in order to investigate the methylation status of CpG sites in non-genital cutaneous warts. Methods: Genomic DNA was extracted from 24 paired epidermal samples of warts and normal skin. DNA samples were bisulfite converted and underwent genome-wide methylation profiling using the Infinium MethylationEPIC BeadChip Kit. Results: From a total of 844,234 CpG sites, 56,960 and 43,040 CpG sites were found to be hypo-and hypermethylated, respectively, in non-genital cutaneous warts. The most differentially methylated CpG sites in warts were located within the C10orf26, FAM83H-AS1, ZNF644, LINC00702, GSAP, STAT5A, HDAC4, NCALD, and EXOC4 genes. Conclusion: Non-genital cutaneous warts exhibit a unique CpG methylation signature.

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HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cells

Cited by 13 publications

References 31 publications

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

An ErbB Lineage Co-Regulon Harbors Potentially Co-Druggable Targets for Multimodal Precision Therapy in Head and Neck Squamous Cell Carcinoma

Genome-wide identification of methylated CpG sites in nongenital cutaneous warts

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