TAL1 mediates imatinib-induced CML cell apoptosis via the PTEN/PI3K/AKT pathway

Wu, Yifan; Hu, Yanyun; Yu, Xibao; Zhang, Yikai; Huang, Xin; Chen, Shaohua; Li, Yangqiu; Zeng, Chengwu

doi:10.1016/j.bbrc.2019.08.164

Cited by 11 publications

(9 citation statements)

References 32 publications

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“…PI3K signaling pathway covers a wide and complicated network critical for the regulation of protein expression [41][42][43], and a series of factors belonging to different downstream functional pathways is associated with the pathway, for example, GSK3β, FOXO3A, caspase-9, and P53, which are involved in cell apoptosis and tumor suppression [44][45][46][47][48][49]; therefore, inhibition of a specific subunit is considered safer than inhibition of several nonspecific targets that operate together in PI3K-associated signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Zhang

Wang

et al. 2020

Mol Cancer

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Background: PI3K/AKT is a vital signaling pathway in humans. Recently, several PI3K/AKT inhibitors were reported to have the ability to reverse cancer multidrug resistance (MDR); however, specific targets in the PI3K/AKT pathways and the mechanisms associated with MDR have not been found because many of the inhibitors have multiple targets within a large candidate protein pool. AKT activation is one presumed mechanism by which MDR develops during cancer treatment. Methods: The effects of inhibiting PI3K 110α and 110β by BAY-1082439 treatment and CRISPR/Cas9 knockout were examined to determine the possible functions of BAY-1082439 and the roles of PI3K 110α and 110β in the reversal of MDR that is mediated by the downregulation of P-gp and BCRP. Inhibition of AKT with GSK-2110183 showed that the downregulation of P-gp and BCRP is independent of generalized AKT inactivation. Immunofluorescence, immunoprecipitation, MTT, flow cytometry and JC-1 staining analyses were conducted to study the reversal of MDR that is mediated by P-gp and BCRP in cancer cells. An ATPase assay and a structural analysis were also used to analyze the potential mechanisms by which BAY-1082439 specifically targets PI3K 110α and 110β and nonspecifically influences P-gp and BCRP. Results: By inhibiting the activation of the PI3K 110α and 110β catalytic subunits through both the administration of BAY-1082439 and the CRISPR/Cas9 deletion of Pik3ca and Pik3cb, the ATP-binding cassette transporters P-gp/ ABCB1 and BCRP/ABCG2 were downregulated, thereby reestablishing the drug sensitivity of human epidermoid carcinoma and non-small cell lung cancer (NSCLC) MDR cells. Inhibition of AKT did not reverse the MDR mediated by P-gp or BCRP. The ABC family proteins and AKT may play MDR-enhancing roles independently. Conclusions: The reversal of the dual functions of ABC-transporter-mediated and AKT-activation-enhanced MDR through the inhibition or knockout of PI3K 110α or 110β promises to improve current strategies based on combined drug treatments to overcome MDR challenges.

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Section: Discussionmentioning

confidence: 99%

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Zhang

Wang

et al. 2020

Mol Cancer

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“…Secondly, PTEN plays critical roles in regulating not only hematopoietic stem cell activity through a Niche-dependent mechanism, but also hematopoiesis and leukemogenesis [341][342][343]. Furthermore, TAL1, c-Jun, EZH2, TRIM22, ETV6/RUNX1, miR-7, -22, -26b, -103, -125b, -126, -139-5p, -181c, -193a, -628, and -3142, as well as LncRNA HULC, UCA1, linc00239 and LINC00265 control leukemogenesis, proliferation, apoptosis or chemoresistance via PI3K/AKT pathway [344][345][346][347][348][349][350][351][352][353][354][355][356][357][358][359][360][361][362][363]. Hereafter, PI3K/AKT pathway inhibition is regarded as a therapeutic approach [364,365] followed by the preclinical studies in leukemia cells [366,367] in spite of the upregulated expression of P2RY14 in acute leukemia cells resistant to PI3K/ mTOR inhibition [368].…”

Section: (Nct01002248; Nct01476137; Nct00881946) (Tables 2 and 3)mentioning

confidence: 99%

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

et al. 2020

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Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/ AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.

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“…Additionally, NR4A1 promote tau hyperphosphorylation by GSK3 signaling (89). TAL1 is an apoptosis factor and it plays its role by regulating of PTEN and eventually inhibiting PI3K signaling pathway (90).…”

Section: Discussionmentioning

confidence: 99%

Evaluation role of miR-124 in neurodegenerative diseases: literature review and in silico analysis

Amini

Bibak

Afshar

et al. 2021

Preprint

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Neurodegenerative diseases (ND) are characterized by loss of function and structure of neurons. NDs like Alzheimer's disease (AD) and Parkinson's disease (PD) have high burden on the society and patients. Currently microRNAs (miRNAs) approach is growing. miRNAs express in different tissues, especially in the central neuron systems (CNS). miRNAs have a dynamic role in the CNS among this miRNAs, miR-124 significantly express in the CNS. Studies on miR-124 have shown that miR-124 improves ND. In this study, we evaluated the role of miR-124 in the ND by literature review and in silico analysis. We used Pubmed database to find miR-124 function in the Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease and amyotrophic lateral sclerosis. To better understand the role of miR-124 in the neurons, RNA-seq data form miR-124-deleted neuronal cells extracted from GEO database and analyzed in Galaxy platform. According literature review miR-124 attenuates inflammation and apoptosis in the ND by target NF-kb signaling pathway and regulation of BAX/BCL-2. miR-124 targets BACE1 and decreases level of Aβ. RNA-seq data showed miR-124 downregulation, an increase in chemokine gene like CCL1 and cytokine-cytokine receptor-interaction, as well as MAPK-signaling pathway. Our study shows that miR-124 can be promising therapeutic approaches to ND.

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TAL1 mediates imatinib-induced CML cell apoptosis via the PTEN/PI3K/AKT pathway

Cited by 11 publications

References 32 publications

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Evaluation role of miR-124 in neurodegenerative diseases: literature review and in silico analysis

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