Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis

Senyuk, Vitalyi; Zhang, Yunyuan; Liu, Yang; Ming, Ming; Premanand, Kavitha; Zhou, Lan; Chen, Ping; Chen, Jianjun; Rowley, Janet D.; Nucifora, Giuseppina; Qian, Zhijian

doi:10.1073/pnas.1302645110

Cited by 70 publications

(61 citation statements)

References 47 publications

(65 reference statements)

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“…This study was also consistent with study performed by Senyuk et al (21) that showed that low expression of miR-9 has leukemogenic effect in ectopic viral integration -1(EV-1) mutated AML. The study showed that miR-9 binds to specific sites causing under expression of genes called FOXO1 and FOXO3 that regulate the cell cycle and in case of under expression of miR-9,these genes are up regulated causing AML through increased rate of cell cycle consequently, increasing proliferation of myeloid precursors.…”

Section: Discussionsupporting

confidence: 82%

Expression of micro RNA-9 in Patients with Acute Myeloid Leukemia and its Impact on Treatment Strategy

Youssef

Ismail²,

Attia³

et al. 2018

The Egyptian Journal of Hospital Medicine

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Background: Acute myeloid leukemia (AML) is a malignant disorder of hematopoietic tissue. It is one of the most common malignancies in adults. It is characterized by its heterogeneous and complex nature that includes chromosomal, genetic and epigenetic abnormalities. MicroRNAs have been described to be one of the epigenetic regulators in AML. Objective: The present study focused on measuring expression levels of miR-9 in de novo AML patients. 30 bone marrow samples were collected from patients attending at Hematology and Oncology Unit of Aldemerdash Hospitals.MiR-9 expression levels were measured using real time PCR. These expression levels were compared to 30 adult healthy volunteers. Patients and Methods: The present study was carried out in medical oncology and Clinical Pathology Departments of Ain Shams University and National Research Centre, Egypt during the period between September 2017 and April 2018. Results: Statistical analysis of the results showed that miR-9 was significantly down regulated in AML patients in comparison to controls. It is also significantly correlated to platelet count. Regarding diagnostic performance, this study showed that miR-9 has weak diagnostic performance but regarding screening function, it has perfect sensitivity but weak specificity so it can be used as an excluding test. Conclusion: This study showed reduction of miR-9 in bone marrow of AML patients and opened the horizon for future studies on diagnostic and screening performance of miR-9 to be performed on larger scale and different ethnic groups.

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Section: Discussionsupporting

confidence: 82%

Expression of micro RNA-9 in Patients with Acute Myeloid Leukemia and its Impact on Treatment Strategy

Youssef

Ismail²,

Attia³

et al. 2018

The Egyptian Journal of Hospital Medicine

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“…Most interestingly, miR-9 overexpression phenocopied the effect of curcumin treatment, impairing Akt activation and FOXO1 phosphorylation. A recent report shows that FOXO1 is a direct target of miR-9 in hematopoietic cells (Senyuk et al, 2013). Taken together, these data suggest that miR-9 mediates the suppression of Akt/FOXO1 axis by curcumin in ovarian cancer cells.…”

Section: Discussionsupporting

confidence: 60%

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

Zhao¹,

Zhang²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin (10-60 μM) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

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“…The pluripotent stem cells are capable of differentiation to form any of the elements of blood, but overproliferation by these cells can lead to a condition called blood cancer or leukemia (Prasanthi et al, 2010;Li et al, 2012). This case, unregulated and abnormal white blood cells division leads to production of large number of immature blood cells (blasts), leading to impairment of various body functions, resulting in different clinical manifestations often seen in leukemia patients (Jemal et al, 2008;Senyuk et al, 2012). The exact cause of most RESEARCH ARTICLE…”

Section: Introductionmentioning

confidence: 99%

Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1 (t 12; 21) in Underdeveloped Countries of the Region

Iqbal

2014

Asian Pacific Journal of Cancer Prevention

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TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.

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Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis

Cited by 70 publications

References 47 publications

Expression of micro RNA-9 in Patients with Acute Myeloid Leukemia and its Impact on Treatment Strategy

Expression of micro RNA-9 in Patients with Acute Myeloid Leukemia and its Impact on Treatment Strategy

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1 (t 12; 21) in Underdeveloped Countries of the Region

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