Lip-1 induces cell cycle arrest, apoptosis, and pyroptosis in K562 cells
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ABSTRACT:
PROVIDER: PRJNA843318 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19437500_1.fastq.gz | Fastqsanger.gz | |||
| SRR19437500_2.fastq.gz | Fastqsanger.gz | |||
| SRR19437501_1.fastq.gz | Fastqsanger.gz | |||
| SRR19437501_2.fastq.gz | Fastqsanger.gz | |||
| SRR19437502_1.fastq.gz | Fastqsanger.gz |
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Project description:summary (1)Objective: To investigate the antileukemic role of Lip-1 in K562 leukemia cells. (2)Methods: We performed CCK-8, flow cytometry, microscopy, western blotting assay, next generation sequencing, PCR assays to evaluate the effect of Lip-1 in K562 leukemia cells. (3)Results: Lip-1 inhibited K562 cell proliferation in a dose- and time-dependent manner. RNA sequencing revealed several pathways that were affected by Lip-1, such as the G1/S transition of the mitotic cell cycle and extrinsic or intrinsic apoptotic signaling pathways. The results of flow cytometry indicated that Lip-1 arrests the cell cycle. K562 cells were characterized by swelling and plasma membrane rupture. The expression of the hallmark of pyroptosis, the cleaved N-terminal GSDME, increased. Endoplasmic reticulum stress and autophagy were involved in Lip-1-induced cell death. (4)Conclusion：Lip-1 induces cell cycle arrest, apoptosis, and secondary pyroptosis in K562 leukemia cells, which provides new hope for the treatment of leukemia.
2022-05-31 | GSE205036 | GEO
Project description:Cannabidiol (CBD) showed antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells (K562 cells). A consolidated DARTS (Drug Affinity Response Target Stability) and t-LIP-MRM (targeted- Limited Proteolysis-Multiple Reaction Monitoring Mass spectrometry) platform was applied to unveil the interactome of CBD and to shed light on its mechanism of action. Both approaches point to the identification of DNA topoisomerase 2-alpha (TOP2A) as a major CBD target in K562 cells.
2024-01-26 | PXD036650 | Pride
Project description:Leukemia is a fatal hematopoietic disorder with a poor prognosis. Drug resistance is inevitable after the long‑term use of chemotherapeutic agents. Liproxstatin‑1, commonly known as a ferroptosis inhibitor, has never been reported to have anticancer effects. In the present study, the antileukemic role of liproxstatin‑1 in K562 leukemia cells was investigated. Liproxstatin‑1 inhibited K562 cell proliferation in a dose‑ and time‑dependent manner. RNA sequencing revealed several pathways that were affected by liproxstatin‑1, such as the G1/S transition of the mitotic cell cycle and extrinsic or intrinsic apoptotic signaling pathways. The results of flow cytometry indicated that liproxstatin‑1 arrests the cell cycle at the G1 phase, and even at the G2/M phase. p21WAF1/CIP1, a cyclin‑dependent kinase inhibitor, was upregulated. It was also determined that liproxstatin‑1 induced BAX and TNF‑α expression, which was accompanied by cleavage of caspase‑3 and PARP. The caspase‑3‑specific inhibitor z‑DEVD‑FMK rescued some of the apoptotic cells. Interestingly, K562 cells were characterized by swelling and plasma membrane rupture when treated with a high concentration of liproxstatin‑1, which was inconsistent with the typical apoptotic appearance. Thus, it was hypothesized that apoptosis‑mediated pyroptosis occurs during liproxstatin‑1‑induced cell death. The expression of the hallmark of pyroptosis, the cleaved N‑terminal GSDME, increased. Additionally, it was observed that endoplasmic reticulum stress and autophagy were involved in liproxstatin‑1‑induced cell death. Collectively, liproxstatin‑1 induced cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 leukemia cells, which provides new hope for the treatment of leukemia.
| S-EPMC9450809 | biostudies-literature
Project description:Background: Nephroblastoma, also known as Wilms’ tumor (WT), is an embryonic malignant tumor and one of the most common malignant tumors in the abdominal region of children. Previous studies have demonstrated that aquaporin 1 (AQP1), a highly expressed channel protein in the kidneys, is closely associated with various diseases and also plays a significant role in tumorigenesis and progression. However, the exact role and underlying mechanisms of AQP1 in the occurrence and development of nephroblastoma remain unclear. Methods: After overexpression of AQP1, cell proliferation was assessed using the CCK-8 proliferation assay and EdU staining. Flow cytometry was employed to detect cell apoptosis, and Western blotting (WB) analysis was conducted to validate the expression of relevant protein markers. mRNA Sequencing (mRNA-Seq) was performed on WT cells with AQP1 overexpression to predict and characterize the associated mechanisms. Transmission electron microscopy was utilized to observe changes in the ultrastructure of WT cells undergoing apoptosis and pyroptosis following AQP1 overexpression. Functional in vivo validation was conducted through animal experiments. Results: We validated at both in vitro and in vivo levels that overexpression of AQP1 inhibited cell proliferation and promoted cell apoptosis and pyroptosis. mRNA-Seq analysis of WT cells with AQP1 overexpression suggested that these effects might be mediated through the inhibition of the JAK-STAT signaling pathway, which was further experimentally validated. Additionally, we discovered that overexpression of AQP1 activated the classical pyroptosis signaling pathway dependent on Caspase-1, thereby promoting pyroptosis in WT. Conclusion: These findings highlight the significant functional role of AQP1 in the pathobiology of nephroblastoma, providing novel insights into the development of this disease. Moreover, these results offer new perspectives on the potential therapeutic targeting of AQP1 as a treatment strategy for nephroblastoma.
2024-02-14 | GSE247460 | GEO
Project description:Background: Tyrosine kinase inhibitor (TKI) resistance is a significant factor exacerbating the burden on chronic myeloid leukemia (CML) patients and impacting clinical efficacy. The main goal is to offer new insights into overcoming drug resistance in treating CML. Methods: (IM) resistant K562/IM cells were generated using gradient induction. Responses to IM, lycorine, and autophagy modulators were assessed using CCK-8. Protein expression of Beclin-1, Atg5, LC3, Caspase-3, P62, Bax, Bcl-2, and P-gp was detected using Western blot. Lycorine-induced apoptosis and cell cycle changes were evaluated through flow cytometry, while autophagy alterations were detected using Monodansylcadaverine(MDC) staining. In the K562/IM mice model, Non-obese diabetic severe combined immunodeficent(NOD-SCID) mice were subcutaneously inoculated with K562/IM cells. After 17 days of lycorine injection, assessments included tumor size, Hematoxylin-eosin(HE) staining, and Ki67 expression. Results: After 72 hours of IM treatment, K562/IM cells showed a 55.86-fold increase in drug resistance compared to K562 cells. Lycorine treatment for 24 hours inhibited cell proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in both K562 and K562/IM cells. MDC staining indicated reduced autophagy in K562/IM cells, mitigated by lycorine. In vivo experiments demonstrated reduced tumor size and Ki67 proliferation index in the lycorine treatment group (K562+L, K562/IM+L) compared to the control group, particularly in the drug-resistant group. However, no significant change in Ki67 was observed in the K562 group after lycorine treatment. Conclusion: In summary, K562/IM cells displayed heightened autophagy levels compared to K562 cells. Lycorine effectively impeded the proliferation of K562/IM cells through diverse mechanisms, including reduced autophagy, enhanced apoptosis, and induced cell cycle arrest.
2024-05-20 | GSE267522 | GEO
Project description:Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPβ) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPβ mRNA. The truncated C/EBPβ LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPβ LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPβ knockin mice that constitutively express only the C/EBPβ LIP isoform from its own locus. Our data show that deregulated C/EBPβ LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPβ LIP supports a protumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/ EBPβ LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPβ LIP isoform.
2014-12-16 | GSE53770 | GEO
Project description:In response to stress, the p53 tumor suppressor induces arrest or apoptosis by transcriptionally regulating genes that mediate these processes. It has been proposed that the levels of p53 can influence the choice between these different outcomes, but the mechanisms involved are not clear. To gain mechanistic understanding of this p53-dependent cell fate decision, we generated a p53 inducible system that allowed tight regulation of p53 expression in human mammary epithelial cells. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Using microarray and chromatin immunoprecipitation analysis, we showed that low and high levels of p53 bind to and activate the same set of pro arrest and pro apoptotic target genes, induced to lower and higher levels, respectively. We propose that the cell fate decision between arrest and apoptosis in these cells is determined by a higher threshold required for p53 dependent apoptosis. We suggest that high level p53 activation is crucial in order to achieve maximum efficacy of p53 targeted cancer therapies.
2011-07-19 | E-GEOD-30753 | biostudies-arrayexpress
Project description:Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPM-NM-2) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPM-NM-2 mRNA. The truncated C/EBPM-NM-2 LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPM-NM-2 LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPM-NM-2 knockin mice that constitutively express only the C/EBPM-NM-2 LIP isoform from its own locus. Our data show that deregulated C/EBPM-NM-2 LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPM-NM-2 LIP supports a protumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/ EBPM-NM-2 LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPM-NM-2 LIP isoform. A cohort of C/EBPb LIP heterozygous (+/L) and wild type (+/+) mice were kept over 25 months and animals showing palpable lymphoma were sacrificed. The lymphoma developed spontaneously. For each genotype, 5 lymphoma were used for RNA preparation and gene expression profiling analysis.
2014-12-16 | E-GEOD-53770 | biostudies-arrayexpress
Project description:The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation. We used microarrays to explore the gene expression profiles differentially expressed in influenza-infected bone marrow derived macrophages (BMDM) isolated from Ifnar1-/- and wild-type mice.
2016-08-11 | E-GEOD-77611 | biostudies-arrayexpress
Project description:Fluorinated rhodacyanines induce apoptosis via mitochondrial damage and cell cycle arrest
| PRJNA1056264 | ENA