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Leukemia Stem Cell-Released Microvesicles Promote the Survival and Migration of Myeloid Leukemia Cells and These Effects Can Be Inhibited by MicroRNA34a Overexpression.

Wang Y, Cheng Q, Liu J, Dong M - Stem Cells Int (2016)

Bottom Line: The effect of miR34a transfection on LSC proliferation and the effects of LMVs(miRCtrl) or LMVs(miR34a) on the proliferation, migration, and apoptosis of AML cells (after LSC depletion) were determined.Results showed that (1) LMVs(miRCtrl) promoted proliferation and migration and inhibited apoptosis of AML cells, which were associated with miR34a deficit; (2) transfection of miR34a mimic inhibited LSC proliferation and increased miR34a level in LMVs(miR34a); (3) LMVs(miR34a) produced opposite effects as compared with LMVs(miRCtrl), which were associated with the changes of caspase-3 and Tim-3 levels.In summary, LMVs support AML cell malignance and modulating miR34a could offer a new approach for the management of AML.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, The Affiliated Hospital of Guilin Medical College, Guilin, Guangxi 541001, China.

ABSTRACT
Leukemia stem cells (LSCs) play the major role in relapse of acute myeloid leukemia (AML). Recent evidence indicates that microvesicles (MVs) released from cancer stem cells can promote tumor growth and invasion. In this study, we investigated whether LSCs-released MVs (LMVs) can regulate the malignance of AML cells and whether overexpression of tumor suppressive microRNA (miR), miR34a, is able to interrupt this process. LSCs were transfected with miRNA control (miRCtrl) or miR34a mimic for producing LMVs, respectively, defined as LMVs(miRCtrl) and LMVs(miR34a). The effect of miR34a transfection on LSC proliferation and the effects of LMVs(miRCtrl) or LMVs(miR34a) on the proliferation, migration, and apoptosis of AML cells (after LSC depletion) were determined. The levels of miR34a targets, caspase-3 and T cell immunoglobulin mucin-3 (Tim-3), were analyzed. Results showed that (1) LMVs(miRCtrl) promoted proliferation and migration and inhibited apoptosis of AML cells, which were associated with miR34a deficit; (2) transfection of miR34a mimic inhibited LSC proliferation and increased miR34a level in LMVs(miR34a); (3) LMVs(miR34a) produced opposite effects as compared with LMVs(miRCtrl), which were associated with the changes of caspase-3 and Tim-3 levels. In summary, LMVs support AML cell malignance and modulating miR34a could offer a new approach for the management of AML.

No MeSH data available.


Related in: MedlinePlus

Effects of LMVsmiRCtrl and LMVsmiR34a on AML cell apoptosis. (a) Representative flow cytometric plots of AML cell apoptosis (percentage of FITC-TUNEL positive cells) after coincubation with veh, LMVsmiRCtrl, or LMVsmiR34a. (b) Summarized data of AML cell apoptosis. Data represents mean ± SEM. ∗P < 0.05 versus veh; #P < 0.05 versus LMVsmiRCtrl. Veh: fresh culture medium; LMVsmiRCtrl: LMVs generated from miRCtrl transfected LSCs; and LMVsmiR34a: LMVs generated from miR34a mimic transfected LSCs.
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fig3: Effects of LMVsmiRCtrl and LMVsmiR34a on AML cell apoptosis. (a) Representative flow cytometric plots of AML cell apoptosis (percentage of FITC-TUNEL positive cells) after coincubation with veh, LMVsmiRCtrl, or LMVsmiR34a. (b) Summarized data of AML cell apoptosis. Data represents mean ± SEM. ∗P < 0.05 versus veh; #P < 0.05 versus LMVsmiRCtrl. Veh: fresh culture medium; LMVsmiRCtrl: LMVs generated from miRCtrl transfected LSCs; and LMVsmiR34a: LMVs generated from miR34a mimic transfected LSCs.

Mentions: AML cell apoptosis (Figure 3) was identified by TUNEL staining and analyzed by flow cytometry. The apoptosis in AML cells was decreased after coincubation with LMVsmiRCtrl when compared with veh or LMVsmiR34a (11.29 ± 1.59% versus 26.70 ± 1.90%, P < 0.05 versus veh; 11.29 ± 1.59% versus 24.53 ± 2.30%, P < 0.05 versus LMVsmiR34a; and n = 3). There was no significant difference in apoptosis between veh-treated and LMVsmiR34a-treated AML cells (26.70 ± 1.90% versus 24.53 ± 2.30%, P = 0.63; n = 3). Moreover, the proliferation (Figure 4(a)) and migration abilities (Figure 4(b)) of AML cells were enhanced after coincubation with LMVsmiRCtrl (P < 0.05 versus veh; n = 3) whereas these effects were absent in AML cells coincubated with LMVsmiR34a (P > 0.05 versus veh; n = 3).


Leukemia Stem Cell-Released Microvesicles Promote the Survival and Migration of Myeloid Leukemia Cells and These Effects Can Be Inhibited by MicroRNA34a Overexpression.

Wang Y, Cheng Q, Liu J, Dong M - Stem Cells Int (2016)

Effects of LMVsmiRCtrl and LMVsmiR34a on AML cell apoptosis. (a) Representative flow cytometric plots of AML cell apoptosis (percentage of FITC-TUNEL positive cells) after coincubation with veh, LMVsmiRCtrl, or LMVsmiR34a. (b) Summarized data of AML cell apoptosis. Data represents mean ± SEM. ∗P < 0.05 versus veh; #P < 0.05 versus LMVsmiRCtrl. Veh: fresh culture medium; LMVsmiRCtrl: LMVs generated from miRCtrl transfected LSCs; and LMVsmiR34a: LMVs generated from miR34a mimic transfected LSCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Effects of LMVsmiRCtrl and LMVsmiR34a on AML cell apoptosis. (a) Representative flow cytometric plots of AML cell apoptosis (percentage of FITC-TUNEL positive cells) after coincubation with veh, LMVsmiRCtrl, or LMVsmiR34a. (b) Summarized data of AML cell apoptosis. Data represents mean ± SEM. ∗P < 0.05 versus veh; #P < 0.05 versus LMVsmiRCtrl. Veh: fresh culture medium; LMVsmiRCtrl: LMVs generated from miRCtrl transfected LSCs; and LMVsmiR34a: LMVs generated from miR34a mimic transfected LSCs.
Mentions: AML cell apoptosis (Figure 3) was identified by TUNEL staining and analyzed by flow cytometry. The apoptosis in AML cells was decreased after coincubation with LMVsmiRCtrl when compared with veh or LMVsmiR34a (11.29 ± 1.59% versus 26.70 ± 1.90%, P < 0.05 versus veh; 11.29 ± 1.59% versus 24.53 ± 2.30%, P < 0.05 versus LMVsmiR34a; and n = 3). There was no significant difference in apoptosis between veh-treated and LMVsmiR34a-treated AML cells (26.70 ± 1.90% versus 24.53 ± 2.30%, P = 0.63; n = 3). Moreover, the proliferation (Figure 4(a)) and migration abilities (Figure 4(b)) of AML cells were enhanced after coincubation with LMVsmiRCtrl (P < 0.05 versus veh; n = 3) whereas these effects were absent in AML cells coincubated with LMVsmiR34a (P > 0.05 versus veh; n = 3).

Bottom Line: The effect of miR34a transfection on LSC proliferation and the effects of LMVs(miRCtrl) or LMVs(miR34a) on the proliferation, migration, and apoptosis of AML cells (after LSC depletion) were determined.Results showed that (1) LMVs(miRCtrl) promoted proliferation and migration and inhibited apoptosis of AML cells, which were associated with miR34a deficit; (2) transfection of miR34a mimic inhibited LSC proliferation and increased miR34a level in LMVs(miR34a); (3) LMVs(miR34a) produced opposite effects as compared with LMVs(miRCtrl), which were associated with the changes of caspase-3 and Tim-3 levels.In summary, LMVs support AML cell malignance and modulating miR34a could offer a new approach for the management of AML.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, The Affiliated Hospital of Guilin Medical College, Guilin, Guangxi 541001, China.

ABSTRACT
Leukemia stem cells (LSCs) play the major role in relapse of acute myeloid leukemia (AML). Recent evidence indicates that microvesicles (MVs) released from cancer stem cells can promote tumor growth and invasion. In this study, we investigated whether LSCs-released MVs (LMVs) can regulate the malignance of AML cells and whether overexpression of tumor suppressive microRNA (miR), miR34a, is able to interrupt this process. LSCs were transfected with miRNA control (miRCtrl) or miR34a mimic for producing LMVs, respectively, defined as LMVs(miRCtrl) and LMVs(miR34a). The effect of miR34a transfection on LSC proliferation and the effects of LMVs(miRCtrl) or LMVs(miR34a) on the proliferation, migration, and apoptosis of AML cells (after LSC depletion) were determined. The levels of miR34a targets, caspase-3 and T cell immunoglobulin mucin-3 (Tim-3), were analyzed. Results showed that (1) LMVs(miRCtrl) promoted proliferation and migration and inhibited apoptosis of AML cells, which were associated with miR34a deficit; (2) transfection of miR34a mimic inhibited LSC proliferation and increased miR34a level in LMVs(miR34a); (3) LMVs(miR34a) produced opposite effects as compared with LMVs(miRCtrl), which were associated with the changes of caspase-3 and Tim-3 levels. In summary, LMVs support AML cell malignance and modulating miR34a could offer a new approach for the management of AML.

No MeSH data available.


Related in: MedlinePlus