Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

Chai, Juin Hsien; Zhang, Yong; Tan, Wei; Chng, Wee Joo; Li, Baojie

doi:10.1186/1471-2407-11-512

Cited by 24 publications

(17 citation statements)

References 58 publications

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“…TM inhibitor library, consisting of Wnt, epidermal growth factor receptor, and JAK/STAT inhibitor libraries, we modified the existing qTRAP to suit the screen (36). TA was quantitated using qTRAP, and all data obtained were normalized against the vehicle control, DMSO.…”

Section: Identification Of Signaling Pathway Inhibitors That Preferenmentioning

confidence: 99%

Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer

Zhang

Toh

Lau

et al. 2012

Journal of Biological Chemistry

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169

113

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Background: Telomerase up-regulation is found in about 90% of human cancer specimens and contributes actively to carcinogenesis. Results: ␤-Catenin⅐TCF4 plays an important role in telomerase activation. Conclusion: hTERT is a direct transcriptional target of the Wnt/␤-catenin pathway. Significance: Identifying the function of the Wnt/␤-catenin pathway in telomerase regulation provides better insight into the role of Wnt pathway in carcinogenesis.

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Section: Identification Of Signaling Pathway Inhibitors That Preferenmentioning

confidence: 99%

Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer

Zhang

Toh

Lau

et al. 2012

Journal of Biological Chemistry

Self Cite

169

113

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“…This resistance occurs faster when cells overexpress TERT [69]. Finally, BCR-ABL was proposed to regulate telomerase activity, and this regulation occurs at multiple levels, including transcription, at the post-translational level, and proper localization [70]. In conclusion, BCR-ABL1 might induce or enhance telomerase activity leading to sustained cell proliferation and cell resistance to apoptosis.…”

Section: Mechanisms Of Telomere Maintenancementioning

confidence: 99%

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Samassékou

2013

Cancers

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the t(9;22) translocation. As in most cancers, short telomeres are one of the features of CML cells, and telomere shortening accentuates as the disease progresses from the chronic phase to the blastic phase. Although most individual telomeres are short, some of them are lengthened, and long individual telomeres occur non-randomly and might be associated with clonal selection. Telomerase is the main mechanism used to maintain telomere lengths, and its activity increases when CML evolves toward advanced stages. ALT might be another mechanism employed by CML cells to sustain the homeostasis of their telomere lengths and this mechanism seems predominant at the early stage of leukemogenesis. Also, telomerase and ALT might jointly act to maintain telomere lengths at the chronic phase, and as CML progresses, telomerase becomes the major mechanism. Finally, CML cells display an altered nuclear organization of their telomeres which is characterized by the presence of high number of telomeric aggregates, a feature of genomic instability, and differential positioning of telomeres. CML represents a good model to study mechanisms responsible for dynamic changes of individual telomere lengths and the remodeling of telomeric nuclear organization throughout cancer progression.

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“…As a typical CML cell line, K562 cells presented t(9:22) (38); thus, the chromosome location of the differentially expressed microRNAs was further examined. Several differentially regulated microRNAs in K562-derived MVs, including miR-27b, miR-24, miR-23b and miR-126*, were located in chromosome 9.…”

Section: Resultsmentioning

confidence: 99%

Comparison of microRNA expression profiles in K562-cells-derived microvesicles and parental cells, and analysis of their roles in leukemia

Chen

Xiong

2016

Oncology Letters

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Microvesicles (MVs) are 30-1,000-nm extracellular vesicles that are released from a multitude of cell types and perform diverse cellular functions, including intercellular communication, antigen presentation, and transfer of proteins, messenger RNA and microRNA (also known as miR). MicroRNAs have been demonstrated to be aberrantly expressed in leukemia, and the overall microRNA expression profile may differentiate normal blood cells vs. leukemia cells. MVs containing microRNAs may enable intercellular cross-talk in vivo. This prompted us to investigate specific variations of microRNA expression patterns in MVs derived from leukemia cells. The present study examined the microRNA expression profile of MVs from chronic myeloid leukemia K562 cells and that of MVs from normal human volunteers' peripheral blood cells. The potential targets of the differentially expressed microRNAs were predicted using computational searches. Bioinformatic analyses of the predicted target genes were performed for further evaluation. The present study analyzed microRNAs of MVs derived from leukemia and normal cells, and characterized specific microRNAs expression. The results revealed that MVs derived from K562 cells expressed 181 microRNAs of the 888 microRNAs assessed. Further analysis revealed that 16 microRNAs were downregulated, while 7 were upregulated in these MVs. In addition, significant differences in microRNA expression profiles between MVs derived from K562 cells and K562 cells were identified. The present results revealed that 77 and 122 microRNAs were only expressed in MVs derived from K562 cells and in K562 cells, respectively. There were 104 microRNAs co-expressed in MVs derived from K562 cells and in K562 cells. Target gene-related pathway analyses demonstrated that the majority of the dysregulated microRNAs were involved in pathways associated with leukemia, particularly the mitogen-activated protein kinase (MAPK) and the p53 signaling pathways. By further conducting microRNA gene network analysis, the present study revealed that the miR-15a/b, miR-16, miR-17 and miR-30 families were likely to play a role in the regulation of the MAPK signaling pathway. Since K562 cells presented the t(9;22) translocation, the current study further examined the predicted function of 12 microRNAs located in chromosomes 9 [Homo sapiens (hsa)-let-7a, hsa-let-7f, miR-126, miR-126*, miR-23b, miR-24, miR-27b and miR-7] and 22 (hsa-let-7b, miR-1249, miR-130b and miR-185), which were expressed both in MVs derived from K562 cells and in K562 cells. The present study identified microRNAs of MVs from leukemia and normal cells, and characterized the expression of specific microRNAs. The current study is also the first to identify and characterize distinct microRNA expression between MVs derived from K562 cells and K562 cells. These findings highlight that a number of microRNAs from leukemia-derived MVs may contribute to the development of hematopoietic malignancies. Further investigation may reveal the function of these differentially expressed mic...

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Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

Cited by 24 publications

References 58 publications

Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer

Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Comparison of microRNA expression profiles in K562-cells-derived microvesicles and parental cells, and analysis of their roles in leukemia

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