KIF11 and its inhibitor SB-743921 inhibit acute myeloid leukaemia (AML) by blocking the cell cycle
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ABSTRACT:
PROVIDER: PRJNA1231385 | ENA |
REPOSITORIES: ENA
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Project description:Acute myeloid leukaemia (AML) is a highly heterogeneous haematological malignancy with limited prognostic improvement despite evolving therapeutic strategies.KIF11 is a member of the kinesin family and a microtubule-associated motility protein that plays a key role in spindle dynamics during cellular mitosis and is overexpressed in leukaemias including AML. Studies have shown that inhibition of KIF11 leads to spindle pole collapse, which prevents chromosome segregation and leads to cell death; this identifies KIF11 as a potential therapeutic target.SB-743921, a novel selective inhibitor of KIF11, has shown anti-tumour activity in a variety of cancers, including breast, lung, and cholangiocarcinoma. Our study shows that SB-743921 can effectively inhibit the proliferation of AML cells and induce cell cycle arrest, thereby hindering tumour growth. In vitro experiments showed that SB-743921 exhibited significant cytotoxicity against several AML cell lines, and its IC50 value indicated that these cells were very sensitive to SB-743921. Further in vivo studies in AML mouse models treated with SB-743921 showed that the drug significantly delayed tumour progression while prolonging survival with minimal toxic side effects. In addition, RNA sequencing analysis showed that SB-743921 inhibited tumour cell proliferation by down-regulating key signalling pathways, including MYC, E2F and G2M. These findings suggest that KIF11 plays a crucial role in the onset and progression of AML. As its inhibitor, SB-743921 has significant anti-tumour effects and is an innovative targeted agent for the treatment of AML. This discovery provides new insights into potential clinical applications for the treatment of this challenging malignancy.
2025-08-19 | GSE291010 | GEO
Project description:In the fire ant Solenopsis invicta, a colony queen number is determined by the founding queen's genotypes at the 13 Mb supergene with the non-recombining variants SB and Sb. Single-queen colonies are always headed by SB/SB queens while multiple-queens colonies are always headed by SB/Sb queens. The two variants of the supergene, SB and Sb are completely linked to the two alleles (B and b) of the gene Gp-9. SB/SB and SB/Sb queens differ in many physiological traits including their maturation rate and odor. To explain why SB/SB and SB/Sb queens have different odors, and why SB/SB virgins mature faster and accumulate more fat, we measured expression of ~6000 genes in virgin queens 1 and 11 days after eclosion and in reproductive queens. Keywords: fire ants, Solenopsis invicta, Supergene, queen, Gp-9, social form, maturation, fat storage, queen odor, cuticular hydrocarbon, worker discrimination, monogyne, polygyne, transposon, chemical signaling
2012-11-07 | GSE42062 | GEO
Project description:We want to determine the protein networks that are associated with KIF11 in the presenceor absence of Rab11 in Caco2 cells. We performed immunoprecipitation against KIF11 using an anti-KIF11 antibody in control and Rab11 knockdown Caco2 cells In addition, we included samples of no antibody control to assess background binding.
2023-06-05 | PXD042335 | Pride
Project description:Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in acentrosomal spindle bipolarization and homologous chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region, where merotelic kinetochore-microtubule attachments are favored to form. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and reveal a spatially differential requirement for homologous chromosome biorientation within the spindle.
2025-07-01 | GSE284383 | GEO
Project description:In the fire ant Solenopsis invicta, a colony queen number is determined by the founding queen's genotypes at the 13 Mb supergene with the non-recombining variants SB and Sb. Single-queen colonies are always headed by SB/SB queens while multiple-queens colonies are always headed by SB/Sb queens. The two variants of the supergene, SB and Sb are completely linked to the two alleles (B and b) of the gene Gp-9. SB/SB and SB/Sb queens differ in many physiological traits including their maturation rate and odor. To explain why SB/SB and SB/Sb queens have different odors, and why SB/SB virgins mature faster and accumulate more fat, we measured expression of ~6000 genes in virgin queens 1 and 11 days after eclosion and in reproductive queens. Keywords: fire ants, Solenopsis invicta, Supergene, queen, Gp-9, social form, maturation, fat storage, queen odor, cuticular hydrocarbon, worker discrimination, monogyne, polygyne, transposon, chemical signaling Six-condition experiment: 1-day-old SB/SB virgins, 1-day-old SB/Sb virgins, 11-day-old SB/SB virgins, 11-day-old SB/Sb virgins, SB/SB reproductive queens, SB/Sb reproductive queens. Biological replicates: 8 for 1-day-old SB/SB virgins and 1-day-old SB/Sb virgins that were collected in 2008; 8 for 1-day-old SB/SB virgins, 1-day-old SB/Sb virgins that were collected in 2009; 7 for 11-day-old SB/SB virgins and 11-day-old SB/Sb virgins that were collected in 2008; 8 for 11-day-old SB/SB virgins and 11-day-old SB/Sb virgins that were collected in 2009; 8 for SB/SB and SB/Sb reproductive queens (only collected in 2009). Samples were labeled with Cy3 and were compared to the same common reference RNA labeled with Cy5. Samples from 2008 were hybridized on the microarrays batch I and samples from 2009 were hybridized on the microarrays batch J.
2012-11-07 | E-GEOD-42062 | biostudies-arrayexpress
Project description:High-throughput sequencing is performed to identify the genes whose expression levels were altered when KIF11 is downregulated by lentiviruses-mediated shRNA in HepG2 cells.
2023-07-30 | GSE238164 | GEO
Project description:Antimony (Sb) pollution, especially released from mining activities has already been widely recognized as a global concern. To gauge strategies for the remediation of an Sb-contaminated ecosystem, the exploration of native microbiota Sb(III) resistance mechanism is of great significance. Acinetobacter is one of the bacterial genera abundantly thriving in Sb(III)-contaminated environments, the scientific elaboration of Sb(III)-resistance mechanisms of Acinetobacter is imperative. Proteomics experiment was performed (Acinetobacter johnsonii JH7 with and without Sb(III) addtion) to probe its pattern of proteins change under Sb(III) stress. We hope that the mechanisms of Sb(III) resistance of Acinetobacter could be revealed by using iTRAQ this time.
2020-01-20 | PXD017203 |
Project description:The aim of these study is to investiate the expression profile of neuroblastoma SK-N-BE(2) xenografts treated with one single dose of the KIF11 inhibitor 4SC-205 for 24 h. RNASeq libraries were prepared following the TruSeq® Stranded mRNA LT Sample Prep Kit protocol and sequenced on NovaSeq 6000 (Illumina). RNA-seq reads were mapped against human reference genome (GRCh38) using STAR software version 2.5.3a with ENCODE parameters. Genes were quantified using RSEM version 1.3.0. Tumors treated with 4SC-205 presented increased expression of genes involved in the G2/M checkpoint and E2F targets. Genes of mTORC1 pathway were found to be less expressed on treated tumors otherwise. This study demonstrates that KIF11 inhibition using 4SC-205 halts cell cycle progression of cancerous cells of neuroblastoma xenografts.
2022-02-06 | GSE166984 | GEO
Project description:Transcriptional profiling of primary human malignant B cells from patients with chronic lymphocytic leukaemia (CLL), comparing untreated CLL cells with CLL cells that have been treated 24h with 200nM mithramycin. Mithramycin intercalates into GC-rich regions of DNA to inhibit binding of the transcription factor SP1. The goal of this experiment is to gain understanding of the genes regulated by SP1 in primary CLL cells.
2022-12-14 | GSE210348 | GEO
Project description:Sb contaminated soil Metagenomic assembly
| PRJNA1268697 | ENA