Gene expression profile of K562 treated with the combination of imatinib and miR-342-5P
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PROVIDER: PRJNA720424 | ENA |
REPOSITORIES: ENA
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Project description:To determine the specific gene expression of imatinib in CML cells with or without miR-342-5P expression, gene array analysis was performed.
2021-10-13 | GSE171659 | GEO
Project description:In order to indetify new target genes of miR-92a-1-5p in chronic myeloid leukemia, K562 cells carrying the BCR::ABL1 fusion gene were transiently transfected with miR-92a mimic or scramble and treated with imatinib. RNA was sequenced to identify genes expressed under imatinib treatment and downregulated after miR-92a-1-5p overexpression.
2024-10-11 | GSE278906 | GEO
Project description:Inhibition of deregulated protein kinases by small molecule drugs has evolved into a major therapeutic strategy for the treatment of human malignancies. Imatinib mesylate has emerged as the leading compound to treat chronic myeloid leukemia (CML), through its inhibition of Bcr- Abl tyrosine kinases, and other cancers. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new BCR-ABL inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib showed large interest since the introduction of the nilotibin. To identify the cellular pathways affected by new synthesized compounds, we applied mass spectrometry together with stable isotope labeling by amino acids in cell culture (SILAC) for the comparative study of protein expression in K562 cells that were untreated or treated with imatinib and imatinib derivates. Further, the global proteome of the K562 cells treated with imatinib were quantitatively compared with the cells treated with the new compounds. This study enriched our knowledge about direct cellular targets of kinase selective drugs. Further the results offered important new knowledge for gaining insights into the structural effects of action of the new compounds. Samples were analyzed on a longer column (30cm) and a longer gradient (180min). Raw data files were processed with Mascot distiller 2.3. The mgf files were searched with Mascot daemon 2.3. The quantification was also done by Mascot Distiller. All data was stored in ms_lims. The manual validation of false peptide ratios was done with Rover (part of ms_lims). Fixed modifications: none. Variable modifications: acetylation of peptide N-terminus, pyroglutamate formation of N-terminal glutamine, methionine oxidation. Enzyme: trypsine with one missed cleavage allowed. Precursor mass tolerance: 10 ppm. Peptide fragment mass tolerance: 0.5 Da Quantitation method: SILAC arginine and lysine +6 Da. Overview of the 17 different analyses: B SK23 vs DMSO C Y22 vs DMSO D SK20 vs DMSO E Y18 vs DMSO I SK20 vs DMSO K Y18 vs DMSO O Y22 vs DMSO R Imatinib vs Water Z Imatinib vs Water J SK20 vs Imatinib M SK23 vs Imatinib N Y22 vs Imatinib P SK23 vs Imatinib Q Y18 vs Imatinib S Y22 vs Imatinib T SK20 vs Imatinib Y Y18 vs Imatinib
2014-06-30 | PXD000216 | Pride
Project description:Chronic myeloid leukemia is a malignant hematopoietic disorder distinguished by a presence of BCR-ABL fused oncogene with constitutive kinase activity. Although targeted therapy by tyrosine kinase inhibitors (TKI) markedly improved patient´s survival and quality of life, development of drug resistance remains a critical issue for a subset of patients. The most common mechanism of TKI resistance in CML patients is a mutation in BCR-ABL gene which makes oncogenic Bcr-Abl protein insensitive to TKI therapy. Mutation independent mechanisms of TKI resistance are less elucidated, but exosomes, extracellular vesicles excreted from normal and tumor cells were recently linked with cancer progression and drug resistance. We used an imatinib-sensitive CML cell line K562 and derived an imatinib-resistant subline K562IR by prolonged cultivation of cells in presence of imatinib. We demonstrated that exosomes isolated from K562IR cells are internalized by K562 cells and increase their survival in presence of 2µM imatinib. To characterize the exosomal cargo and to identify resistance-associated marker proteins, we performed a deep proteomic analysis of exosomes from both cell sublines using label free quantification (LFQ). In total, we identified over 3000 exosomal proteins including 31 proteins differentially abundant in exosomes derived from K562IR cells. Among the differential proteins were three massively upregulated membrane proteins in K562IR exosomes with surface localization: IFITM3, CD146, CD36. We verified the massive upregulation of the three proteins in K562IR exosomes and also in K562IR cells. Using flow cytometry, we further demonstrated potential of CD146 as cell surface marker associated with imatinib resistance in K562 cells.
2024-10-24 | PXD019283 | Pride
Project description:Genes downregulated by miR-92a-1-5p overexpression in K562 cells treated with imatinib.
| PRJNA1169551 | ENA
Project description:The molecular mechanisms behind the miR-342-5p-induced HER2 pathway regulation are not known. Here, we aimed to further investigate the role of miR-342-5p in HER2 driven breast cancer cells. Transfected cells were incubated for 24 hours, and total RNA were run on mRNA arrays.
2017-12-21 | GSE108324 | GEO
Project description:LncRNAs play a crucial role in regulating the progression of NSCLC, making them potential targets for cancer diagnosis and treatment. Therefore, identifying new lncRNAs as therapeutic target and comprehending their underlying regulatory mechanisms are crucial for treating NSCLC. In this study, we found that glioblastoma down-regulated RNA (GLIDR) was increased in non-response NSCLC patients with the primary treatment, and GLIDR was also highly expressed in NSCLC patients. We used bioinformatic analysis and luciferase assays to identify that microRNA-342-5p (miR-342-5p) directly targets GLIDR. MiR-342-5p overexpression inhibits NSCLC cell proliferation, migration, and invasion, whereas miR-342-5p inhibition promotes NSCLC malignancy, which can be rescued by suppressing GLIDR. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) was identified as a downstream target of miR-342-5p. PPARGC1A inhibition significantly suppresses NSCLC malignancy, whereas overexpression promotes it. The results also revealed that GLIDR overexpression reduced PPARGC1A inhibition by miR-342-5p, and increased PPARGC1A expression reversed the inhibition of NSCLC malignancies caused by decreased GLIDR. To the best of our knowledge, we are the first to discover that GLIDR promotes NSCLC progression by sponging miR-342-5p to regulate PPARGC1A expression, presenting that GLIDR act as a potential therapeutic target in NSCLC.
2023-11-16 | GSE243455 | GEO
Project description:Background: Characterized by high incidence, mutilation, and death rate, acute ischemic stroke (AIS) has threatened people’s health seriously. Therefore, there is an urge need for early diagnosis and effective treatment of AIS. The purpose of this study was to clarify the regulatory role and potential molecular mechanism of miR-342-5p and circRNA_0008146 in AIS. Materials and Methods: Small RNA sequencing analysis was performed to screen differentially expressed miRNAs between the AIS and control group. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. The circRNA_0008146 and miRNA expression levels were detected by quantitative real-time PCR. Assay kits were used to determine Fe2+ levels and assess a battery of oxidative stress indicators, including ROS, MDA, LPO, SOD, and GSH/GSSG. The content of ACSL4 was measured by Western blot. The neurobehavioral manifestation was evaluated using the modified Neurological Severity (mNSS) Score, rotarod test, and corner test. TTC staining was employed to detect cerebral infarction volume. Nissl staining was adapted to detect histological change and neuronal damage. Results: RNA sequencing analysis revealed miR-342-5p was significantly downregulated in the plasma of AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic-reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. CircRNA_0008146 acted as a sponge of miR-342-5p, and overexpression of circRNA_0008146 increased brain damage in stroke mice. CircRNA_0008146 contributed to ferroptosis in cerebral infraction via sponging miR-342-5p to regulate ACSL4. Conclusion: CircRNA_0008146/miR-342-5p/ACSL4 axis regulate ferroptosis after cerebral ischemia-reperfusion, which may be a potential therapeutic target for ischemic stroke.
2024-08-08 | GSE254322 | GEO
Project description:Transcriptional profiling of K562-r comparing control untreated human leukemia cells with human leukemia cells treated with AMN107 and ATO individually or combined.Four timepoints included are 3h,12h,24h,48h, covering the whole time window of K562-r cells responsing to the drug treatment.At the combination of 1.5uM ATO and 8uM AMN107, K562-r cells have the most significant coordinated effects (the apoptosis rate at 72h was 56.41% compared to 12.23% in ATO alone and 29.8% in AMN107 alone.). We studied gene expression series in K562-r cells with or without drug treatments by cDNA microarray analysis. Many genes involved in endoplasmic reticulum (ER) stress signaling, including ATF3, DDIT3, HERPUD1, HSPA5, XBP1 and TXNDC12, were highly up-regulated within 12 h of co-treatment, suggesting that the combination of ATO with AMN107 induced an ER stress response leading to apoptosis later on. Other ER-stress markers like the JNK pathway, which bridges the ER-stress and apoptosis, have been activated. Knock down the initiator of JNK partially alleviate the effects of apoptosis (p<0.05). Co-administering AMN107 and arsenic trioxide, inducing apoptosis via the ER-stress, indicates a novel therapy alternative for the imatinib induced secondary resistance. 17-condition experiment, untreated K562-r vs. Drug-treated K562-r cells, including 4 time points, for each point the untreated and 1.5uM ATO treated,8uM AMN107 treated and both 1.5uM ATO and 8uM AMN107 treated, independently grown and harvested. One replicate per array. Untreated K562-r_0h used to counteracting the background.
2010-12-30 | E-GEOD-24946 | biostudies-arrayexpress
Project description:Treatment with demethylating agents in combination with tyrosine kinase inhibitors have shown improved molecular responses and survival benefits in patients with TKI-resistant or advanced-phase CML. However, little is known regarding underlying mechanism of the combination anti-tumor effect of demethylating agents and tyrosine kinase inhibitors. To analyze the combination effect, we have compared gene expression profiles among chronic myeloid leukemia (CML) cell lines (K562, KBM5) treated with imatinib (IM), a new demethylating agent, OR-2100 (OR21), and these combination therapy.
2020-09-09 | GSE157620 | GEO