Abstract:
:Cisplatin-based chemotherapy is the standard treatment of choice for head and neck squamous cell carcinoma (HNSCC). The efficiency of platinum-based therapies is directly influenced by the development of tumor resistance. Multiple signaling pathways have been linked to tumor resistance, including activation of nuclear factor kappa B (NFκB). We explore a novel mechanism by which NFκB drives HNSCC resistance through histone modifications. Post-translational modification of histones alters chromatin structure, facilitating the binding of nuclear factors that mediate DNA repair, transcription, and other processes. We found that chemoresistant HNSCC cells with active NFκB signaling respond to chemotherapy by reducing nuclear BRCA1 levels and by promoting histone deacetylation (chromatin compaction). Activation of this molecular signature resulted in impaired DNA damage repair, prolonged accumulation of histone γH2AX and increased genomic instability. We found that pharmacological induction of histone acetylation using HDAC inhibitors prevented NFκB-induced cisplatin resistance. Furthermore, silencing NFκB in HNSCC induced acetylation of tumor histones, resulting in reduced chemoresistance and increased cytotoxicity following cisplatin treatment. Collectively, these findings suggest that epigenetic modifications of HNSCC resulting from NFκB-induced histone modifications constitute a novel molecular mechanism responsible for chemoresistance in HNSCC. Therefore, targeted inhibition of HDAC may be used as a viable therapeutic strategy for disrupting tumor resistance caused by NFκB.
journal_name
FEBS Open Biojournal_title
FEBS open bioauthors
Almeida LO,Abrahao AC,Rosselli-Murai LK,Giudice FS,Zagni C,Leopoldino AM,Squarize CH,Castilho RMdoi
10.1016/j.fob.2013.12.003subject
Has Abstractpub_date
2013-12-30 00:00:00pages
96-104issn
2211-5463pii
S2211-5463(13)00077-6journal_volume
4pub_type
杂志文章相关文献
FEBS Open Bio文献大全abstract::A local tissue-specific renin-angiotensin system (local RAS) has been identified in many organs. However, no report has described the role of a local RAS in the hypertrophic differentiation of chondrocytes. To examine the role of a local RAS in the hypertrophic differentiation, we activated angiotensin II type 1 recep...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2013.07.001
更新日期:2013-07-04 00:00:00
abstract::Curcumin is a polyphenolic phytonutrient that has antineurodegenerative properties. In this study, we investigated the anti-amyloidogenic properties of curcumin. Following incubation with curcumin, intrinsic tryptophan fluorescence emission of apolipoprotein (apo) A-I was strongly quenched. At the same time, curcumin ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12372
更新日期:2018-01-10 00:00:00
abstract::Megakaryoblastic leukemia 1 (MKL1) is a member of the MKL family of serum response factor (SRF) coactivators. Here we have identified three rat MKL1 transcripts: two are homologues of mouse MKL1 transcripts, full-length MKL1 (FLMKL1) and basic, SAP, and coiled-coil domains (BSAC), the third is a novel transcript, MKL1...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2013.09.001
更新日期:2013-09-07 00:00:00
abstract::Hsp90 is essential for maintaining the activity of numerous signaling factors, and plays a key role in cellular signal transduction networks. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an ansamycin antibiotic that binds to Hsp90 and inhibits its function. HaCaT human keratinocytes were used to investigate the ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2012.03.002
更新日期:2012-03-25 00:00:00
abstract::Centrins are members of the EF-hand family of calcium-binding proteins, which are highly conserved among eukaryotes. Centrins bind to several cellular targets, through a hydrophobic triad. However, the W(1)xxL(4)xxxL(8) triad in XPC (Xeroderma Pigmentosum Group C protein) is found in the reverse orientation, as in the...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2013.11.005
更新日期:2013-12-05 00:00:00
abstract::Shiga toxin (Stx) causes fatal systemic complications. Stx induces apoptosis, but the mechanism of which is unclear. We report that Stx induced rapid reduction of short-lived anti-apoptotic proteins followed by activation of caspase 9 and the progression of apoptosis. Proteasome inhibitors prevented the reduction of a...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2015.06.005
更新日期:2015-06-12 00:00:00
abstract::Post-transcriptional regulation of cytokine production is crucial to ensure appropriate immune responses. We previously demonstrated that poly-rC-binding protein-1 (PCBP1) can act as a trans-acting factor to stabilize transcripts encoding sortilin, which mediates cytokine trafficking. Here, we report that PCBP2, which...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12794
更新日期:2020-03-01 00:00:00
abstract::Osteosarcoma is a malignant bone tumor, and clinically detectable metastases can be detected in ~ 15-20% of patients when they seek medical advice; patients with metastatic disease have extremely poor prognosis. Here, we examined the involvement of the microRNA miR-505 in osteosarcoma. Eighty-four patients seeking tre...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12868
更新日期:2020-07-01 00:00:00
abstract::Goji berries have been used as food and medicine for millennia. Due to their high morphological similarity, fruits of two distinct species belonging to the family Solanaceae, Lycium barbarum (LB) and Lycium chinense (Chinese boxthorn), are usually marketed together as goji berries, but nearly 90% of all commercially a...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12910
更新日期:2020-08-01 00:00:00
abstract::Human type 2 diabetes is associated with β-cell apoptosis, and human islets from diabetic donors are ∼80% deficient in PAK1 protein. Toward addressing linkage of PAK1 to β-cell survival, PAK1-siRNA targeted MIN6 pancreatic β-cells were found to exhibit increased caspase-3 cleavage, cytosolic cytochrome-C and the pro-a...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2012.09.001
更新日期:2012-09-08 00:00:00
abstract::Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects. Therefore, there is...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2015.08.004
更新日期:2015-08-11 00:00:00
abstract::A plant-derived Enterococcus mundtii 15-1A, that has been previously isolated from Brassica rapa L. subsp. nipposinica (L.H. Bailey) Hanelt var. linearifolia by our group, possesses two kinds of l-lactate dehydrogenase (l-LDH): LDH-1 and LDH-2. LDH-1 was activated under low concentration of fluctose-1,6-bisphosphate (...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2014.08.006
更新日期:2014-09-06 00:00:00
abstract::Human melanoma is a highly malignant tumor originating from cutaneous melanocytes. The noncoding RNA microRNA (miR)-21-5p has been reported to be expressed at high levels in malignant melanocytic skin tissues, but its potential functional role in melanoma remains poorly understood. Here, we explored the cellular effec...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12819
更新日期:2020-05-01 00:00:00
abstract::Soft cheese with white rind lacks essential fatty acids (EFAs), and as a result its long-term consumption may lead to various kinds of cardiovascular and cerebrovascular diseases, such as hyperlipidemia, hypertension, and atherosclerosis. Geotrichum candidum is a dimorphic yeast that plays an important role in the rip...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12553
更新日期:2018-12-06 00:00:00
abstract::Micro-exons are a set of ultrashort exons with lengths ≤ 51 nucleotides. Our previous study revealed that micro-exons were enriched in AP2 domains and K-box domains, which are crucial components of AP2/ERF (APETALA2/ethylene-responsive element-binding protein) and MADS-box (an acronym of MCM1, AGAMOUS, DEFICIENS and S...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12990
更新日期:2020-12-01 00:00:00
abstract::Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO)...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2013.08.008
更新日期:2013-09-07 00:00:00
abstract::Human STIL (SCL/TAL1 interrupting locus) protein maintains centriole stability and spindle pole localisation. It helps in recruitment of CENPJ (Centromere protein J)/CPAP (centrosomal P4.1-associated protein) and other centrosomal proteins. Mutations in STIL protein are reported in several disorders, especially in der...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2012.09.003
更新日期:2012-09-25 00:00:00
abstract::Thymic stromal lymphopoietin (TSLP) has been identified as a crucial inflammatory cytokine in immune homeostasis. Previous studies have reported conflicting effects of TSLP on sepsis in mice, and the effect of TSLP on sepsis in humans has not been investigated. In this study, we used the ELISA to measure serum levels ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12746
更新日期:2019-12-01 00:00:00
abstract::PSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interac...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2014.05.005
更新日期:2014-06-06 00:00:00
abstract::Immunoglobulin (Ig) A nephropathy (IgAN) is the most common glomerulonephritis, which is characterized by the deposition of IgA antibody in the glomerulus. Systematic dissection of immune composition may contribute to a better understanding of the alternations in the immune system in IgAN. To this end, here we applied...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.13006
更新日期:2020-12-01 00:00:00
abstract::The yeast cyclins Cln1 and Cln2 are very similar in both sequence and function, but some differences in their functionality and localization have been recently described. The control of Cln1 and Cln2 cellular levels is crucial for proper cell cycle initiation. In this work, we analyzed the degradation patterns of Cln1...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12157
更新日期:2016-12-14 00:00:00
abstract::Identifying conserved binding motifs is an efficient way to study protein-ligand recognition. Most 3D binding motifs only contain information from the protein side, and so motifs that combine information from both protein and ligand sides are desired. Here, we propose an algorithm called LibME (Ligand-binding Motif Ex...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12150
更新日期:2016-11-30 00:00:00
abstract::We previously reported a profound augmentation in the hepatic levels of a pro-inflammatory precursor, arachidonic acid (AA), during liver tumorigenesis. Here, we report a critical role of the induced reactive oxygen species (ROS)-mediated cellular activation of a protein cross-linking enzyme, transglutaminase 2 (TG2),...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12511
更新日期:2018-09-11 00:00:00
abstract::Acute lung injury (ALI) is accompanied by overactivation of multiple pro-inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)-induced ALI is unknown. In this study, CYP1A1 was shown to ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12977
更新日期:2020-09-15 00:00:00
abstract::Sorafenib is an inhibitor of a variety of tyrosine kinase receptors used to treat various cancers including hepatocellular, renal cell and thyroid carcinoma. It has been shown to change various targets associated with osteosarcoma, but the detailed mechanism remains unclear. In order to identify key genes, enriched pa...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12428
更新日期:2018-04-24 00:00:00
abstract::The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat) as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins fo...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2014.02.012
更新日期:2014-03-12 00:00:00
abstract::Osteosarcoma, one of the most common malignant bone tumors, is characterized by a high rate of metastasis, and the survival rate of patients with metastatic osteosarcoma is poor. Previous studies have reported that miRNAs often regulate the occurrence and development of various tumors. In this work, we identified miRN...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12824
更新日期:2020-04-01 00:00:00
abstract::Inorganic polyphosphate (polyP) is a linear polymer containing tens to hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. PolyP promotes osteocalcification and bone mineralization in both mouse and human osteoblastic cells. In the present study, we examined the molecular mechanism by whi...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12703
更新日期:2019-09-01 00:00:00
abstract::Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long non-coding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs (...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12802
更新日期:2020-01-27 00:00:00
abstract::Growth hormone receptor (GHR), a member of the class I cytokine receptor family, plays key roles in cancer progression. Recently, GHR has been reported to be associated with breast cancer development, but the molecular mechanism of GHR in this malignancy is not fully understood. To investigate this issue, we stably in...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12816
更新日期:2020-06-01 00:00:00