Abstract:
:Hepatocellular carcinoma (HCC) is a prevalent malignancy with increasing incidence and extremely poor prognosis worldwide. The multi-kinase inhibitor sorafenib is widely used as a first-line systematic treatment agent of advanced hepatocellular carcinoma. However, the benefit of sorafenib in clinical treatment is often impeded by drug resistance. Therefore, it is of critical importance to investigate the molecular mechanisms underlying sorafenib resistance in HCC. The present study shows that expression of the key glycolytic enzyme PFKFB3 is significantly up-regulated in both HCC cell lines and tissues. Thereafter, the expression of PFKFB3 was elevated in hepatocellular carcinoma cell after sorafenib treatment, which was confirmed in Gene Expression Omnibus (GEO) datasets. As predicted, the overexpression of PFKFB3 significantly enhanced HCC cells resistance to sorafenib by decreasing expression of the apoptosis-related molecules as well as apoptotic cells. Additionally, blockage of hypoxia-inducible factor-1α (HIF-1α) restricted the enhancement of PFKFB3. More interestingly, we initially found that exogenous expression of PFKFB3 significantly up-regulated the protein levels of HIF-1α in both SK-Hep-1 and SMMC-7721 cells. Further mechanistic study uncovered that HIF-1α deficiency impaired sorafenib resistance induced by PFKFB3 overexpression in HCC cells. To conclude, here we reveal a previously unrecognised positive feedback loop exists between PFKFB3 and HIF-1α and a novel HIF-1α-dependent role of PFKFB3 in regulating sorafenib resistance in HCC cells, suggesting new potential therapeutic targets for HCC treatment.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Long Q,Zou X,Song Y,Duan Z,Liu Ldoi
10.1016/j.bbrc.2019.03.109subject
Has Abstractpub_date
2019-06-04 00:00:00pages
642-650issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(19)30498-Xjournal_volume
513pub_type
杂志文章abstract::Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we fo...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2013.07.095
更新日期:2013-08-23 00:00:00
abstract::The cDNA encoding human ferrochelatase [EC 4.99.1.1] was isolated from a human placenta cDNA library in bacteriophage lambda gt11 by screening with a radiolabeled fragment of mouse ferrochelatase cDNA. The cDNA had an open reading frame of 1269 base pairs (bp) encoding a protein of 423 amino acid residues (Mr. 47,833)...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(05)80099-3
更新日期:1990-12-14 00:00:00
abstract::There is increasing evidence to suggest that Ca2+-calmodulin dependent protein kinase (CaMK) regulates the sarcoplasmic reticulum (SR) function and thus plays an important role in modulating the cardiac performance. Because intracellular Ca2+-overload is an important factor underlying cardiac dysfunction in a heart di...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/S0006-291X(02)00287-5
更新日期:2002-05-03 00:00:00
abstract::Although it's well known that protein carbonyl (PCO) and advanced glycation end-products (AGEs) levels are elevated in plasma from patients with renal dysfunction, we recently identified patients who had no renal dysfunction but possessed high levels of plasma pentosidine (PEN), which is an AGEs, and low vitamin B6 le...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2015.09.152
更新日期:2015-11-13 00:00:00
abstract::In Escherichia coli, endonuclease III (endo III) repairs the oxidation products of 8-OHGua. However, the corresponding repair enzymes in eukaryotes have not been identified. Here we report that 8-hydroxyguanine (8-OHGua) is highly sensitive to further oxidation. We also show that Ntg2, a functional homolog of endo III...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.5305
更新日期:2001-08-03 00:00:00
abstract::Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As curren...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2008.12.077
更新日期:2009-02-06 00:00:00
abstract::A ferric low-spin species with an anomalously small g3-g1 separation generated by the reaction of Fe(III)tetraphenylporphyrin with t-butylhydroperoxide in the presence of tatramethylammonium hydroxide was characterized by ESR spectroscopy. The reaction kinetics, investigated by monitoring ESR intensity, indicated that...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(86)91023-5
更新日期:1986-03-28 00:00:00
abstract::Multi electrode arrays (MEAs) are increasingly used to detect external field potentials in electrically active cells. Recently, in combination with cardiomyocytes derived from human (induced) pluripotent stem cells they have started to become a preferred tool to examine newly developed drugs for potential cardiac toxi...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2017.01.151
更新日期:2018-03-18 00:00:00
abstract::Monoclonal antibodies against chick embryonic beta-galactoside-binding lectin were obtained. One of the monoclonal antibodies was ineffective in Western blotting and seemed to be unable to bind the SDS-denatured lectin. When the native lectin was dotted on a nitrocellulose filter and subjected to denaturation by treat...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(84)80257-0
更新日期:1984-09-28 00:00:00
abstract::The loss of endothelial function is the initiating factor in the development of diabetic vascular disease. Kinins control endothelial function by the activation of two receptors: the B2 which is constitutively expressed, and the B1 which is highly induced in pathological conditions. In the present study, we observed t...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2006.04.127
更新日期:2006-06-30 00:00:00
abstract::We studied the effect of eotaxin, a novel eosinophil-active CC chemokine with high target cell specificity, on human basophils. Eotaxin induced higher levels of chemotactic response with a lower ED50 compared with RANTES in basophils; half-maximal migration occurred at a concentration of approximately 3 nM. On the oth...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1997.6100
更新日期:1997-02-13 00:00:00
abstract::To study its biological functions, tumor necrosis factor precursor (proTNF) with a molecular size of 26-KDa was obtained as a recombinant protein from Escherichia coli. The recombinant proTNF was successfully accumulated in the insoluble form, corresponding to about 10-15% of total E. coli proteins. Solubilization, ge...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(91)91426-d
更新日期:1991-08-30 00:00:00
abstract::Bolus intravenous injection of arachidonic acid (10 mg/kg) in the rat led to the appearance of hepoxilin A3 in the circulation. The product was assayed as the Me t-BDMSi derivative of its stable trihydroxy product trioxilin A3, by capillary gas chromatography-electron impact mass spectrometry using the stable deuteriu...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(87)80152-3
更新日期:1987-09-30 00:00:00
abstract::Antileukoprotease (ALP) was isolated from bronchial secretion. The amino acid composition as well as the N-terminal sequence were determined. No homology with other low molecular weight proteinase inhibitors was found. ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(85)91676-6
更新日期:1985-04-16 00:00:00
abstract::Homologous species specificity is demonstrated with bovine and human thyroglobulin in which the two terminal sugars of the B carbohydrate chain, sialic acid and galactose have been removed by enzymatic hydrolysis. The species specificity is demonstrated by measuring the ability of the deglycosylated thyroglobulin deri...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(83)90654-x
更新日期:1983-08-12 00:00:00
abstract::ERK8 is the most recent addition for the MAPK family, and its mechanism of activation and function are not yet known, mainly due to the lack of any known physiological stimulator. In this report, we describe the preparation of reagents for the use of a novel method, the ligand interaction scan (LIScan), to study the f...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2010.07.029
更新日期:2010-08-13 00:00:00
abstract::BIK, a member of the Bcl-2 family, has been reported to induce cell apoptosis but the underlying mechanisms are not well delineated. We used siRNA targeting caspase-12 to examine the effect of caspase-12 on apoptosis induced by BIK. In this study, we show that caspase-12 was activated by BIK. With caspase-12 knocked d...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2007.05.175
更新日期:2007-08-10 00:00:00
abstract::Sf9 cells infected with the recombinant mouse CaMKII-alpha (Ca2+/calmodulin dependent kinase II) baculovirus expressed 12-15 mg of MCaMKII-alpha per liter of cells. Approximately 50% of the MCaMKII-alpha activity could be purified using a CaM-Sepharose affinity column. The purified MCaMKII-alpha had a M(rapp) of 50 kD...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(05)80074-9
更新日期:1990-12-14 00:00:00
abstract::Many bacterial respiratory redox enzymes depend on the twin-arginine translocase (Tat) system for translocation and membrane insertion. Tat substrates contain an N-terminal twin-arginine (SRRxFLK) motif serving as the targeting signal towards the translocon. Many Tat substrates have a system specific chaperone - redox...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2015.08.079
更新日期:2015-10-02 00:00:00
abstract::PU.1 is a transcription factor found in macrophages, B cells, neutrophils, and hemopoietic stem cells. In macrophages PU.1 regulates a number of genes, including c-fms, CD11b, CD18, and FcgammaR1b. Previously, in primary macrophages PU.1 binding to the sequence GAGGAA was found to be induced by treatment with bacteria...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.9905
更新日期:1999-01-08 00:00:00
abstract::CD134 (OX40), a member of the tumour necrosis factor receptor family, is expressed on activated T cells and mediates T and B cell costimulation. Its expression is increased after exposure to the thiol-binding compound HgCl2 in BN rats, but not in Lewis rats, in association with induction of a T cell-dependent systemic...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1997.7679
更新日期:1997-11-17 00:00:00
abstract::Total RNA isolated from a rainbow trout (Oncorhynchus mykiss) liver was subjected to RT/PCR using degenerate primers designed from homologous regions amongst cytochrome P450 CYP4 proteins. PCR amplification resulted in a single electrophoretic band which was excised, purified and sequenced directly, using cycle sequen...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1997.6957
更新日期:1997-07-18 00:00:00
abstract::Extracellular signal-regulated kinase (ERK) is one of the key protein kinases that regulate the growth and proliferation in cardiac fibroblasts (CFs). As an energy sensor of cellular metabolism, AMP-activated protein kinase (AMPK) is found recently to be involved in myocardial remodeling. In this study, we investigate...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2008.01.099
更新日期:2008-04-04 00:00:00
abstract::Gastrin is a peptide hormone important in acid regulation, growth of enterochromaffin cells of the oxyntic mucosa, and smooth muscle contractility. We isolated a genomic clone of gastrin from a SV-129 murine genomic library. The murine gastrin gene contains an open reading frame of 101 amino acids. The deduced amino a...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1995.2588
更新日期:1995-11-02 00:00:00
abstract::To test the hypothesis that ferroxidase I (ceruloplasmin) activity is essential for iron mobilization, adult rats were fed a copper sufficient diet with or without the chelating drugs D-penicillamine and triethylenetetramine for 120 days. By day 6 of treatment and for the remainder of the experiment the drug-fed rats ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(83)90441-2
更新日期:1983-05-31 00:00:00
abstract::Long repeated stretches of d(CCG) and tri-nucleotide are crucial mutations that cause hereditary forms of mental retardation (fragile X-syndrome). Moreover, the alternating (CG) di-nucleotide is one of the candidates for Z-DNA conformation. Solution NMR structure of d(CCGCGG)(2) has been solved and is discussed. The d...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(03)00304-8
更新日期:2003-03-28 00:00:00
abstract::Tau plays important roles in the assembly and stabilization of the microtubule structure to facilitate axonal transport in mammalian brain. The intracellular tau aggregates to form paired helical filaments leading to neurodegenerative disorders, collectively called tauopathies. In our previous report, we established a...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2016.06.058
更新日期:2016-08-19 00:00:00
abstract::The immunoglobulin mu intronic enhancer is a potent B cell-specific transcriptional activator. The enhancer is activated by the appropriate combination of transcription factors, amongst which are ets and bHLH proteins. HMGA1 (formerly HMG-I(Y)) is a demonstrated co-activator of the mu enhancer. HMGA1 functions through...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2002.6672
更新日期:2002-03-29 00:00:00
abstract::Binding affinity and selectivity are critical properties of aptamers that must be optimized for any application. The sulforhodamine B binding RNA aptamer (SRB-2) is a somewhat promiscuous aptamer that can bind ligands that vary markedly in shape, size and charge. Here we categorize potential ligands based on their bin...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2020.06.056
更新日期:2020-08-27 00:00:00
abstract::To investigate the functions of key domains of the epidermal growth factor receptor (EGFR), various EGFR-derived peptide sequences were expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins. The purified fusion proteins (GST-TK0-8) were tested as substrates for the tyrosine kinase activities...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(90)91915-f
更新日期:1990-01-15 00:00:00