The Hippo-p53 pathway in megakaryopoiesis

Suraneni, Praveen; Crispino, John D.

doi:10.3324/haematol.2016.156125

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…Further attention has been paid to the role of p53 in hematopoietic stem cell differentiation (28). p53 has been found to regulate the differentiation of megakaryocytes and macrophages (29)(30)(31), specifically mediated megakaryocytic polyploidization and apoptosis (16). A study published in 2012 has shown that PLT count in p53 -/mice is slightly lower than that in wild-type mice, indicating that p53 could alter PLT function in p53-deficient mice (18).…”

Section: Discussionmentioning

confidence: 99%

Trp53 regulates platelets in bone marrow via the PI3K pathway

et al. 2020

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The p53 gene is well known as a key tumor suppressor gene; it is vital for hematopoietic stem cell differentiation and growth. In the present study, the change of platelets (PLTs) in p53 knockout mice (p53-/mice) was investigated. The peripheral blood cell subsets and PLT parameters in p53-/mice were compared with those in age-matched p53 +/+ mice. Bleeding time as well as the alteration of PLT levels, were analyzed with the PLT marker CD41 antibody using flow cytometry. The results revealed that the number of PLTs in p53-/mice was significantly lower than that in p53 +/+ mice. Bleeding time was prolonged in the peripheral blood of p53-/mice compared with that of p53 +/+ mice. Furthermore, the related gene expression of the PI3K signaling pathway in the bone marrow of p53-/mice was shown to be associated with plateletogenesis. PI3K inhibitor (LY294002) was also used to treat p53-/mice, and the results demonstrated that LY294002 revert the change of PLTs in these mice. In summary, PLTs were altered in p53-/mice, and the PI3K signaling pathway was involved in that process, suggesting that the p53-dependent PI3K signaling pathway is involved in thrombocytopenia or PLT diseases. PLT number is reduced in p53 deficiency; however, this reduction could be reverted by inhibiting the PI3K pathway.

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Section: Discussionmentioning

confidence: 99%

Trp53 regulates platelets in bone marrow via the PI3K pathway

et al. 2020

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“…In parallel, LATS1/2 stabilizes p53 by disrupting the MDM2-p53 interaction. In polyploid megakaryocytes, the Hippo-p53 pathway remains off as the reduction in RhoA activity fails to activate LATS1/2, allowing YAP/TAZ to translocate into the nucleus and promoting target gene expression [10]. .…”

Section: Discussionmentioning

confidence: 99%

Absence of miR-378d Promoted The Malignant Phenotype of ESCC Through The AKT-β-Catenin and Hippo-p53 Signaling Pathway

Peng

Liu

et al. 2020

Preprint

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Background: Chemoresistance is an important cause of malignant progression of esophageal squamous cell carcinomas (ESCCs). miR-378d is sharply reduced in paclitaxel (PTX)-resistance esophageal cancer cells by gene-expression profile analysis (RNA-Seq), but the mechanism of miR-378d-mediated tumor progression is unclear. Patients and methods: Herein, we detected miR-378d expression in 596 ESCC patients by in situ hybridization. Results showed that low miR-378d expression was associated with poor prognosis of ESCC patients, and that miR-378d absence enhanced carcinogenesis by promoting chemoresistance, colony formation, EMT, invasion, and metastasis. Results: Furthermore, miR-378d can target downregulated AKT1 expression by binding to the AKT1 mRNA 3′UTR, inactivating the AKT-β-catenin signaling pathway, and reducing the epithelial–mesenchymal transition marker Vimentin and the cancer stem cell marker ALDH1A1. miR-378d silencing in ESCC cells also promoted polyploidy formation in vitro and in vivo, and miR-378d inhibition suppressed the Hippo-p53 signaling pathway. Consequnetly, YAP and TAZ protein accumulated in nuclei and p53 expression decreased, which may promote the formation of ploidy tumor cells. Conclusions: Therefore, low miR-378d expression is a poor prognostic factor of ESCC patients and promotes polyploidy and cancer progression by activating AKT-β-catenin and suppressing the Hippo-p53 signaling pathway.

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