Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA395477 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To compare the global gene expressions between KLF4-expressed AML cells and albendazole-treated AML cells, we conducted gene expression arrays in THP-1 cells lentivirally-transduced with doxycycline-inducible KLF4 or in THP-1 cells treated with albendazole in different concentrations. We identified that albendazole induces prominent differentiation in THP-1 cells through up-regulating KLF4 and DPYSL2A expressions. Considering the guaranteed safety and tolerability of albendazole in humans, this drug could easily be repositioned to AML patients once its anti-tumor efficacy is clarified.
2021-03-09 | GSE101784 | GEO
Project description:Role of DPYSL2A in KLF4-mediated monocytic differentiation in AML cells
| PRJNA395350 | ENA
Project description:MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21), inv(16) or MLL-rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL-rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21) (n=21), inv(16) (n=17) or MLL-rearrangement (n=35) by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases, which also included 12 t(15;17) and 5 t(7;12) samples.
2014-01-01 | E-GEOD-52541 | biostudies-arrayexpress
Project description:To compare the global gene expressions in between KLF4- and DPYSL2A-expressed AML cells, we conducted gene expression arrays in THP-1 cells lentivirally-transduced with doxycycline-inducible KLF4 or DPYSL2A. We identified the pivotal role of KLF4-DPYSL2A axis in differentiating AML cells, which could be theraputically-tageted in conventional therapy-resistant AML patients.
2020-05-31 | GSE101751 | GEO
Project description:MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21), inv(16) or MLL-rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL-rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner.
2014-01-01 | GSE52541 | GEO
Project description:Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
2022-11-09 | PXD038057 |
Project description:Venetoclax (VEN) has transformed the therapy of acute myeloid leukemia (AML), but resistance and relapse are a major challenge. Monocytic differentiation was proposed as a cause of VEN resistance, but clinical and laboratory evidence is conflicting. Here we harness AML patientderived induced pluripotent stem cells (iPSCs) and Genotyping of Transcriptomes (GoT) to interrogate how mutational status and differentiation stage affect VEN sensitivity independently of one another. Findings in primary and iPSC-derived AML stem cells (LSCs) and monocytic blasts, together with clinical trial data, reveal that monocytic blasts are resistant to VEN, in contrast to LSCs, which express high levels of BCL2 and are sensitive, and that it is the latter, but not the former, that determines the clinical outcome. Crucially, N/KRAS-mutant LSCs produce more monocytic blasts, downregulate BCL2 and are resistant to VEN, driving clinical resistance or relapse. We thus provide a unifying mechanistic model of VEN resistance in AML.
2024-08-09 | GSE235206 | GEO
Project description:Analysis of gene expression changes associated with KLF4 expression in the AML cell lines THP1 cells. Resutls demonstrate KLF4 promotes myeloid differentiation in these cells via gene signatures. We also identified KLF4 downstream regulators that are modified in miR-150 and p21 (CDKN1A) CRISPR knockdown cells.
2015-12-17 | GSE73477 | GEO
Project description:Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
2022-12-14 | GSE216305 | GEO
Project description:Vascular smooth muscle cells (VSMCs) within atherosclerotic lesions undergo a phenotypic switching in a KLF4-dependent manner. Glycolysis plays important roles in transdifferentiation of somatic cells, however, it is unclear whether and how KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions. Here, we show that KLF4 upregulation accompanies VSMCs phenotypic switching in atherosclerotic lesions. KLF4 enhances the metabolic switch to glycolysis through increasing PFKFB3 expression. Inhibiting glycolysis suppresses KLF4-induced VSMCs phenotypic switching, demonstrating that glycolytic shift is required for VSMCs phenotypic switching. Mechanistically, KLF4 upregulates expression of circCTDP1 and eEF1A2, both of which cooperatively promote PFKFB3 expression. TMAO induces glycolytic shift and VSMCs phenotypic switching by upregulating KLF4. Our study indicates that KLF4 mediates the link between glycolytic switch and VSMCs phenotypic transitions, suggesting that a previously unrecognized KLF4-eEF1A2/circCTDP1-PFKFB3 axis plays crucial roles in VSMCs phenotypic switching.
2022-12-14 | GSE216303 | GEO