Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators

Zou, Xiaojing; Qu, Mingyi; Fang, Fang; Zeng, Fan; Chen, Lin; Yue, Wen; Xie, Xiaoyan; Pei, Xuetao

doi:10.1155/2017/2320519

Cited by 9 publications

(13 citation statements)

References 28 publications

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“…Therefore, we confirmed that RHOB expression inversely correlated with miR-1915-3p expression. A few previous reports 24 , 25 and our study 26 demonstrated that SCR and ROCK , downstream effectors of RHOB , acted as negative regulators of MK differentiation. Accordingly, we deduced that miR-1915-3p carried by PMPs was transported to target cells and suppressed RHOB expression in target cells, thereby inducing megakaryocytic differentiation and maturation (Supplementary Fig.…”

Section: Resultssupporting

confidence: 63%

“…The Rho/ROCK pathway is well acknowledged as a negative regulator of MK endomitosis and proplatelet formation 24,37 . RHOB activated SCR and ROCK 24,25 , and inhibitors of SCR and ROCK promoted MK differentiation and maturation 26 . Accordingly, PMPs contained high levels of miR-1915-3p and might induce MK differentiation of recipient cells by inhibiting the Rho/ROCK pathway.…”

Section: Discussionmentioning

confidence: 99%

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Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p

Zou²,

Fang

et al. 2020

Nat Commun

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Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.

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Section: Resultssupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p

Zou²,

Fang

et al. 2020

Nat Commun

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“…AURKB is actively involved in mitosis, chromosomal alignment and segregation, formation of the cleavage furrow, and control of checkpoints, and therefore prevents the occurrence of aneuploidy [83,85,86]. In fact, inhibition of AURKB has been found to lead to polyploidy in vitro in both cancer and non-cancer cells [83,84,86,96]. AURKC is the least-studied member of the family.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Protein Kinase Inhibitors with PLK4 Cross-Over Potential in a Pre-Clinical Model of Cancer

Suri

Bailey

Tavares

et al. 2019

IJMS

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Polo-like kinase 4 (PLK4) is a cell cycle-regulated protein kinase (PK) recruited at the centrosome in dividing cells. Its overexpression triggers centrosome amplification, which is associated with genetic instability and carcinogenesis. In previous work, we established that PLK4 is overexpressed in pediatric embryonal brain tumors (EBT). We also demonstrated that PLK4 inhibition exerted a cytostatic effect in EBT cells. Here, we examined an array of PK inhibitors (CFI-400945, CFI-400437, centrinone, centrinone-B, R-1530, axitinib, KW-2449, and alisertib) for their potential crossover to PLK4 by comparative structural docking and activity inhibition in multiple established embryonal tumor cell lines (MON, BT-12, BT-16, DAOY, D283). Our analyses demonstrated that: (1) CFI-400437 had the greatest impact overall, but similar to CFI-400945, it is not optimal for brain exposure. Also, their phenotypic anti-cancer impact may, in part, be a consequence of the inhibition of Aurora kinases (AURKs). (2) Centrinone and centrinone B are the most selective PLK4 inhibitors but they are the least likely to penetrate the brain. (3) KW-2449, R-1530 and axitinib are the ones predicted to have moderate-to-good brain penetration. In conclusion, a new selective PLK4 inhibitor with favorable physiochemical properties for optimal brain exposure can be beneficial for the treatment of EBT.

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“…Then, the mRNA level of p21 and GAPDH was quantified using SYBR Premix ExTaq (TaKaRa, Tokyo, Japan) with the 2 −ΔΔCt method according to the manufacturer's instructions. The primer sequences are shown in Table 33–35 …”

Section: Methodsmentioning

confidence: 99%

Proteomics reveals the function reverse of MPSSS‐treated prostate cancer‐associated fibroblasts to suppress PC‐3 cell viability via the FoxO pathway

et al. 2021

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Prostate cancer‐associated fibroblasts (prostate CAFs) are essential components of the tumor microenvironment and can promote tumor progression through their immunosuppressive functions. MPSSS, a novel polysaccharide purified from Lentinus edodes , has been reported to have anti‐tumor activity. MPSSS could also inhibit the immunosuppressive function of prostate CAFs, which has been demonstrated through that the secretome of MPSSS‐treated prostate CAFs could inhibit the proliferation of T cells. However, how the secretome of MPSSS‐treated prostate CAFs influence prostate cancer progression is still unclear. Interestingly, we found that the low molecular weight (3–100kD) secretome of prostate CAFs (lmwCAFS) could promote the growth of PC‐3 cells, while that of MPSSS‐treated prostate CAFs (MT‐lmwCAFS) could inhibit their growth. We carried out comparative secretomic analysis of lmwCAFS and MT‐lmwCAFS to identify functional molecules that inhibit the growth of PC‐3 cells, and proteomic analysis of lmwCAFS‐treated PC‐3 cells and MT‐lmwCAFS‐treated PC‐3 cells to investigate the underlying molecular mechanism. These analyses suggest that TGF‐β3 from MT‐lmwCAFS may inhibit the growth of PC‐3 cells. The validated experiments revealed that TGF‐β3 from MT‐lmwCAFS activated p21 expression in PC‐3 cells by regulating the FoxO pathway thereby inducing G0/G1 cell cycle arrest of PC‐3 cells. Overall, our data demonstrated that MPSSS reversed the ability of prostate CAFs to suppress the cell viability of PC‐3 cells, which might provide a potential therapeutic strategy to prevent prostate cancer progression.

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Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators

Cited by 9 publications

References 28 publications

Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p

Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p

Evaluation of Protein Kinase Inhibitors with PLK4 Cross-Over Potential in a Pre-Clinical Model of Cancer

Proteomics reveals the function reverse of MPSSS‐treated prostate cancer‐associated fibroblasts to suppress PC‐3 cell viability via the FoxO pathway

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