Abstract：
:Runt-related transcription factor 1 (RUNX1), one subunit of core-binding factors in hematopoiesis and leukemia, was highly expressed in ovarian cancer (OC), but the role of RUNX1 in OC is largely unknown. Since we found that high expression of RUNX1 is correlated with poor survival in patients with OC through bioinformatic analysis of TCGA database, we developed RUNX1-knockout clones by CRISPR/Cas9 technique and discovered that RUNX1 depletion could promote cisplatin-induced apoptosis in OC cells, which was further confirmed by RUNX1 knockdown and overexpression. We also proved that RUNX1 could elevate the expression of BCL2. We then examined a total of 32 candidate miRNAs that might mediate the regulation between RUNX1 and BCL2, of which three miRNAs from the miR-17~92 cluster were found to be negatively regulated by RUNX1. Consistently, our analysis of data from TCGA database revealed the negative correlation between RUNX1 and the cluster. We further confirmed that miR-17~92 cluster could enhance cisplatin-induced apoptosis by directly targeting BCL2 3'UTR. Since rescue experiments proved that RUNX1 could repress cisplatin-induced apoptosis by up-regulating BCL2 via miR-17~92 cluster, combining RUNX1 inhibitor Ro5-3335 and cisplatin showed synergic effect in triggering OC cell apoptosis. Collectively, these findings show for the first time that combinational treatment of cisplatin and RUNX1 inhibitor could be used to potentiate apoptosis of ovarian cancer cells, and reveal the potential of targeting RUNX1 in ovarian cancer chemotherapy.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Xiao L,Peng Z,Zhu A,Xue R,Lu R,Mi J,Xi S,Chen W,Jiang Sdoi
10.1016/j.bcp.2020.114116subject
Has Abstractpub_date
2020-10-01 00:00:00pages
114116eissn
0006-2952issn
1873-2968pii
S0006-2952(20)30352-Xjournal_volume
180pub_type
杂志文章abstract：:The bisindolylmaleimide Ro 31-8220 is a selective inhibitor of protein kinase C. This compound was used to investigate the involvement of protein kinase C in the stimulation of gastric acid secretion by the muscarinic cholinergic receptor on rat isolated parietal cells. The accumulation of the weak base aminopyrine by...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90541-4
更新日期：1993-08-17 00:00:00
abstract：:The inhibition of renal ornithine decarboxylase (ODC) by aminoglycoside antibiotics was characterized in the postmitochondrial fraction of a kidney homogenate from adult pigmented guinea pigs. Enzymatic activity was defined as the rate of decarboxylation of [14C]ornithine sensitive to a specific ODC inhibitor, alpha-d...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90427-3
更新日期：1988-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01519-8
更新日期：2003-02-01 00:00:00
abstract：:The therapeutic efficacy of immunosuppressive agents has been intensively studied for colitis management. We synthesized a series of andrographolide derivatives and reported their structure-activity-relationship and anti-inflammatory activity in our previous studies. Among these derivatives, compound 3b exhibited the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.03.019
更新日期：2019-05-01 00:00:00
abstract：:Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from creatine kinase (CK) elevation to myopathy. The purpose of this study was to explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on mitocho...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.10.005
更新日期：2017-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90490-5
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90326-6
更新日期：1986-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00848-1
更新日期：2002-03-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90595-a
更新日期：1992-03-03 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.09.003
更新日期：2008-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.12.005
更新日期：2019-02-01 00:00:00
abstract：:Estrogen receptor (ER), antiestrogen binding sites (AEBS) and calmodulin (CaM) are potential targets of antiestrogen (AE) action. To analyse further which of these targets are primarily involved in the antiproliferative activity of these drugs against human breast cancers, two cell clones, namely the RTx6 and LY-2 var...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90500-2
更新日期：1994-11-29 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90394-8
更新日期：1989-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(96)00716-2
更新日期：1997-04-25 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.10.008
更新日期：2014-12-15 00:00:00
abstract：:Rats were made vitamin K-deficient by feeding them a diet devoid of vitamin K and by rigorously preventing coprophagy. After one week, circulating prothrombin concentrations were between 5 and 10% of initial values, and various amounts of phylloquinone, menaquinone-4, and menaquinone-9 were given in a single dose eith...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00202-b
更新日期：1995-09-07 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.01.034
更新日期：2010-06-01 00:00:00
abstract：:Nucleoside analogs used in antiviral therapies need to be phosphorylated to their tri-phospho counterparts in order to be active on their cellular target. Human phosphoglycerate kinase (hPGK) was recently reported to participate in the last step of phosphorylation of cytidine L-nucleotide derivatives [Krishnan PGE, La...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.06.012
更新日期：2004-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90189-4
更新日期：1993-06-09 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.01.031
更新日期：2013-04-15 00:00:00
abstract：:The ability of gold coordination complexes to bind to DNA and produce inter-strand cross-links in DNA was assessed in an assay system based on the fluorescence properties of the DNA intercalative dye, ethidium bromide. Results from these studies using a variety of gold(I) and gold(III) complexes suggest that the abili...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90107-3
更新日期：1986-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.07.009
更新日期：2013-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90631-6
更新日期：1993-12-03 00:00:00
abstract：:Prodrug activation gene therapy for cancer involves expressing prodrug-activating enzymes in tumour cells, so they can be selectively killed by systemically administered prodrug. For example, Escherichia colinfsB nitroreductase (E.C. 1.6.99.7)(NTR), sensitises cells to the prodrug CB1954 (5-[aziridin-1-yl]-2,4-dinitro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.07.025
更新日期：2010-01-15 00:00:00
abstract：:Indole-3-carbinol (I3C), found in cruciferous vegetables, has been shown to suppress tumorigenesis at estrogen-responsive sites. This effect may be mediated through modification by I3C of the cytochrome P450 (CYP) complement and activities leading to estrogen detoxication. In this study, we examined the effects of 4- ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01190-5
更新日期：2002-08-01 00:00:00
abstract：:This mini-review addresses the effect of glycosylation and phosphorylation on the conformational alterations of the epidermal growth factor receptor (EGFR). Based on studies with full-length and truncated EGFRs, we propose a model to suggest that receptor-receptor self-association, which occurs in the truncated recept...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(00)00425-1
更新日期：2000-10-15 00:00:00
abstract：:Phosphodiesterase inhibitors were used as a tool to manipulate cellular nucleotide levels in vitro and in vivo. The lipopolysaccharide (LPS)-induced release of tumor necrosis factor alpha (TNF-alpha) from mouse peritoneal macrophages was inhibited by prostaglandin E2 with an IC50 of 0.05 microM and by dibutyryl-cAMP w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90219-m
更新日期：1993-06-22 00:00:00
abstract：:Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' trea...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90577-5
更新日期：1985-08-01 00:00:00
abstract：:Despite the steadily increased numbers of formyl peptide receptor (FPR) ligands identified over the years, few have been characterized in studies using animal disease models and even less have entered clinical trials in human subjects. A small-molecule compound, Act-389949, was however recently tested in a phase I cli...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.04.030
更新日期：2019-08-01 00:00:00
abstract：:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a commercially available chemical reagent. Although little has been known about its biological effects, recently MPTP has been reported to cause irreversible Parkinson's disease-like symptoms in humans and in monkeys. We describe here another pharmacologic effect ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90593-8
更新日期：1984-10-01 00:00:00
