Ribosomal protein S14 silencing inhibits growth of acute myeloid leukemia transformed from myelodysplastic syndromes via activating p53

Wang, Li; Luo, Jie; Nian, Qing; Xiao, Qing; Zhou, Yang; Liu, Lin

doi:10.1179/1607845413y.0000000127

Cited by 14 publications

(11 citation statements)

References 23 publications

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“…Moreover, the overexpression of Rplp1 alone bypasses replicative senescence in murine cells and cooperates with oncogenic Ras to transform NIH3T3 cells and immortalize MEFs. Additionally, S3A, S14, L5, and L41 were reported to regulate malignant transformation (Naora et al, 1998;Wang et al, 2010Wang et al, , 2014Wool, 1996). All of these studies suggest that aberration of RP expression contributes to neoplastic transformation and cancer progression, although detailed mechanisms remain to be elucidated.…”

Section: Neoplastic Transformationmentioning

confidence: 94%

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Xiong

Sun

2016

Sci. China Life Sci.

103

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Ribosomal proteins (RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia and 5q-syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health. ribosomal protein, tumorigenesis, genomic integrity, ribosomal stress, p53, MDM2 Citation:Xu, X., Xiong, X., and Sun, Y. (2016). The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity. Sci China Life Sci 59, 656 -672.

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Section: Neoplastic Transformationmentioning

confidence: 94%

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Xiong

Sun

2016

Sci. China Life Sci.

103

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“…The human MDS/AML cell line SKM-1 was provided by Professor Jianfeng Zhou (Department of Hematology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China). Cells were maintained in RPMI-1640 (HyClone, Logan, UT, USA) supplemented with 10% heat-inactivated foetal bovine serum (FBS; Gibco-BRL, Invitrogen Life Technologies, Inc., Carlsbad, CA, USA) ( 15 ).…”

Section: Methodsmentioning

confidence: 99%

Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species

Wei

Xiao

Kuang

et al. 2015

Molecular Medicine Reports

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Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and a high risk of progression to acute myeloid leukaemia (AML). Fucoidan, a complex sulphated polysaccharide isolated from the cell wall of brown seaweeds, has recently attracted attention for its multiple biological activities and its potential as a novel candidate for cancer therapy. In the present study, the anti-cancer activity of fucoidan was investigated in the MDS/AML cell line SKM-1. Fucoidan inhibited proliferation, induced apoptosis and caused G1-phase arrest of the cell cycle in SKM-1 cells as determined by a cell counting kit 8 assay and flow cytometry. Furthermore, reverse transcription quantitative polymerase chain reaction and western blot analyses indicated that treatment with fucoidan (100 µg/ml for 48 h) activated Fas and caspase-8 in SKM-1 cells, which are critical for the extrinsic apoptotic pathway; furthermore, caspase-9 was activated via decreases in phosphoinositide-3 kinase/Akt signaling as indicated by reduced levels of phosphorylated Akt, suggesting the involvement of the intrinsic apoptotic pathway. In addition, fucoidan treatment of SKM-1 cells resulted in the generation of reactive oxygen species (ROS) as determined by staining with dichloro-dihydro-fluorescein diacetate. These results suggested that the mechanisms of the anti-cancer effects of fucoidan in SKM-1 are closely associated with cell cycle arrest and apoptotic cell death, which partly attributed to the activation of apoptotic pathways and accumulation of intracellular ROS. Our results demonstrated that Fucoidan inhibits proliferation and induces the apoptosis of SKM-1 cells, which provides substantial therapeutic potential for MDS treatment.

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“…Lentivirus was produced in 293T cells as described previously (13). SKM-1 and K562 cells at exponential stage were plated in 6-well plates (5x10 4 cells/well), transduced with SPAG6-shRNA lentivirus or NC-shRNA lentivirus in the presence of 5 µg/ml polybrene at MOI (multiplicities of infection) of 100 and 20, respectively, as described (14). After 5 days, the transduction efficiency was evaluated by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

SPAG6 silencing inhibits the growth of the malignant myeloid cell lines SKM-1 and K562 via activating p53 and caspase activation-dependent apoptosis

Yang

Wang

Luo

et al. 2014

International Journal of Oncology

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SPAG6, which is a novel cancer-testis antigen, is overexpressed in myeloid malignancies. Previously, SPAG6 was found in UPD (uniparental disomy) region of myeloid cell DNA from MDS patients and reported that SPAG6 may be a predictive marker of minimal residual disease in pediatric acute myeloid, but the biological role of SPAG6 in myeloid malignancies remains unclear. The present study was undertaken to determine the expression and functional significance of SPAG6 in malignant myeloid hematologic cell lines. A short hairpin RNA (shRNA) targeting SPAG6 was designed that could specifically inhibit SPAG6 expression at the mRNA and protein levels when introduced into the malignant myeloid hematologic cell lines SKM-1 and K562. The results from flow cytometry and CCK-8 assays showed that SPAG6 silencing inhibited the proliferation of SKM-1/K562 by inducing apoptosis. Furthermore, SPAG6 silencing resulted in activation of caspase-3, -9 and -8 and upregulated the mRNA and protein expression of p53 and PTEN. Then, we subcutaneously inoculated the monoclonal cells into NOD/SCID mice to establish xenograft models, and we found that the SPAG6-shRNA lentivirus dramatically inhibited tumor growth and increased apoptosis in vivo. These findings demonstrate that SPAG6 might have a role in malignant myeloid hematologic cell proliferation and apoptosis by regulating caspase proteins and p53, suggesting that SPAG6 may be a potential therapeutic target.

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Ribosomal protein S14 silencing inhibits growth of acute myeloid leukemia transformed from myelodysplastic syndromes via activating p53

Abstract: These findings indicate that partial silencing of RPS14 inhibits the proliferation of MDS/AML cells, and RPS14 may negatively regulate p53 activation in MDS/AML cells.

Cited by 14 publications

References 23 publications

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species

SPAG6 silencing inhibits the growth of the malignant myeloid cell lines SKM-1 and K562 via activating p53 and caspase activation-dependent apoptosis

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