Promyelocytic Leukemia Gene Functions and Roles in Tumorigenesis

Imani-Saber, Zeinab; Ghafouri‐Fard, Soudeh

doi:10.7314/apjcp.2014.15.19.8019

Cited by 8 publications

(5 citation statements)

References 77 publications

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“…Herein, we identified promyelocytic leukemia (PML) as a novel miR-762 target gene associated with the ability of this miRNA to regulate endothelial cell and keratinocyte migration. PML plays a role in many important cellular processes, including tumor suppression, apoptosis, transcriptional regulation, DNA damage response, senescence, and viral defense mechanisms [ 43 – 45 ]. Herein, we confirmed that PML was a direct miR-762 target, and we found that overexpressing PML was sufficient to reverse the beneficial impact of miR-762 on cellular migration.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from human induced pluripotent stem cells-derived keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells migration

Yang

Liu

et al. 2022

J Nanobiotechnol

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Background The use of keratinocytes derived from induced pluripotent stem cells (iPSCs-KCs) may represent a novel cell therapy strategy for burn treatment. There is growing evidence that extracellular vesicles, including exosomes, are primary mediators of the benefits of stem cell therapy. Herein, we thus explored the effects of exosomes produced by iPSCs-derived keratinocytes (iPSCs-KCs-Exos) in a model of deep second-degree burn wound healing and evaluated the mechanistic basis for the observed activity. Methods iPSCs-KCs-Exos were isolated from conditioned medium of iPSCs-KCs and verified by electron micrograph and size distribution. Next, iPSCs-KCs-Exos were injected subcutaneously around wound sites, and its efficacy was evaluated by measuring wound closure areas, histological examination, and immunohistochemistry staining. The effects of iPSCs-KCs-Exos on proliferation and migration of keratinocytes and endothelial cells in vitro were assessed by EdU staining, wound healing assays, and transwell assay. Then, high-throughput microRNA sequencing was used to explore the underlying mechanisms. We assessed the roles of miR-762 in iPSCs-KCs-Exos-induced regulation of keratinocytes and endothelial cells migration. Furthermore, the target gene which mediated the biological effects of miR-762 in keratinocytes and endothelial cells was also been detected. Results The analysis revealed that iPSCs-KCs-Exos application to the burn wound drove the acceleration of wound closure, with more robust angiogenesis and re-epithelialization being evident. Such iPSCs-KCs-Exos treatment effectively enhanced endothelial cell and keratinocyte migration in vitro. Moreover, the enrichment of miR-762 was detected in iPSCs-KCs-Exos and was found to target promyelocytic leukemia (PML) as a means of regulating cell migration through a mechanism tie to integrin beta1 (ITGB1). Conclusion These results thus provide a foundation for the further study of iPSCs-KCs-Exos as novel cell-free treatments for deep second-degree burns. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Exosomes from human induced pluripotent stem cells-derived keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells migration

Yang

Liu

et al. 2022

J Nanobiotechnol

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“…PML has multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis. These roles have implied that it could be a suitable therapeutic target for cancer therapy (Imani-Saber and Ghafouri-Fard, 2014). Although multiple studies have indicated loss of PML in gastric cancer, the exact mechanism of such loss of function is not clear.…”

Section: Discussionmentioning

confidence: 99%

In Silico Interaction and Docking Studies Indicate a New Mechanism for PML Dysfunction in Gastric Cancer and Suggest Imatinib as a Drug to Restore Function

Imani-Saber

Ghafouri‐Fard²

2015

Asian Pacific Journal of Cancer Prevention

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Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2.

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“…PML is a major component of PML-NBs, which are nuclear matrix-associated domain and spheres of 0.1-1.0 μm in diameter found in most cell lines and many tissues [4]. In normal circumstances and particularly, in response to cellular stress, PML-NBs undergo significant changes in the number, size, and position [5].…”

Section: Interaction Of Promyelocytic Leukemia/p53 Affects Signal Tramentioning

confidence: 99%

Interaction of promyelocytic leukemia/p53 affects signal transducer and activator of transcription-3 activity in response to oncostatin M

Lim

Choi

Park

et al. 2020

Korean J Physiol Pharmacol

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Promyelocytic leukemia (PML) gene, through alternative splicing of its Cterminal region, generates several PML isoforms that interact with specific partners and perform distinct functions. The PML protein is a tumor suppressor that plays an important role by interacting with various proteins. Herein, we investigated the effect of the PML isoforms on oncostatin M (OSM)-induced signal transducer and activator of transcription-3 (STAT-3) transcriptional activity. PML influenced OSMinduced STAT-3 activity in a cell type-specific manner, which was dependent on the p53 status of the cells but regardless of PML isoform. Interestingly, overexpression of PML exerted opposite effects on OSM-induced STAT-3 activity in p53 wild-type and mutant cells. Specifically, overexpression of PML in the cell lines bearing wild-type p53 (NIH3T3 and U87-MG cells) decreased OSM-induced STAT-3 transcriptional activity, whereas overexpression of PML increased OSM-induced STAT-3 transcriptional activity in mutant p53-bearing cell lines (HEK293T and U251-MG cells). When wild-type p53 cells were co-transfected with PML-IV and R273H-p53 mutant, OSM-mediated STAT-3 transcriptional activity was significantly enhanced, compared to that of cells which were transfected with PML-IV alone; however, when cells bearing mutant p53 were co-transfected with PML-IV and wild-type p53, OSM-induced STAT-3 transcriptional activity was significantly decreased, compared to that of transfected cells with PML-IV alone. In conclusion, PML acts together with wild-type or mutant p53 and influences OSM-mediated STAT-3 activity in a negative or positive manner, resulting in the aberrant activation of STAT-3 in cancer cells bearing mutant p53 probably might occur through the interaction of mutant p53 with PML.

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Promyelocytic Leukemia Gene Functions and Roles in Tumorigenesis

Cited by 8 publications

References 77 publications

Exosomes from human induced pluripotent stem cells-derived keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells migration

Exosomes from human induced pluripotent stem cells-derived keratinocytes accelerate burn wound healing through miR-762 mediated promotion of keratinocytes and endothelial cells migration

In Silico Interaction and Docking Studies Indicate a New Mechanism for PML Dysfunction in Gastric Cancer and Suggest Imatinib as a Drug to Restore Function

Interaction of promyelocytic leukemia/p53 affects signal transducer and activator of transcription-3 activity in response to oncostatin M

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