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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

The particle number and miR-34a level of LMVs, LMVsmiRCtrl, and LMVsmiR34a. (a) Representative NTA plots of MV size distribution (left) and concentration (right). (b) qRT-PCR analysis of miR-34a level in LMVs, LMVsmiRCtrl, and LMVsmiR34a. Data represents mean ± SEM. ∗P < 0.05 versus LMVs; #P < 0.05 versus LMVsmiRCtrl. LMVs represent MVs generated from LSCs without transfection; LMVsmiRCtrl represent MVs generated from LSCs transfected with miRCtrl; and LMVsmiR34a represent MVs generated from LSCs transfected with miR34a mimic.
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fig2: The particle number and miR-34a level of LMVs, LMVsmiRCtrl, and LMVsmiR34a. (a) Representative NTA plots of MV size distribution (left) and concentration (right). (b) qRT-PCR analysis of miR-34a level in LMVs, LMVsmiRCtrl, and LMVsmiR34a. Data represents mean ± SEM. ∗P < 0.05 versus LMVs; #P < 0.05 versus LMVsmiRCtrl. LMVs represent MVs generated from LSCs without transfection; LMVsmiRCtrl represent MVs generated from LSCs transfected with miRCtrl; and LMVsmiR34a represent MVs generated from LSCs transfected with miR34a mimic.

Mentions: As shown in Figure 2(a), NTA analysis showed that the number of LMVsmiR34 was higher than that of LMVs or LMVsmiRCtrl, although there were no significant changes in their size distribution. More interestingly, the expression of miR34a in LMVs was displayed in the same pattern as their parent LSCs. As shown in Figure 2(a), qRT-PCR assay showed that the level of miR34a in LMVsmiR34 was much higher than that of LMVs or LMVsmiRCtrl. There was no significant difference of miR34a level between LMVs and LMVsmiRCtrl.


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)

The particle number and miR-34a level of LMVs, LMVsmiRCtrl, and LMVsmiR34a. (a) Representative NTA plots of MV size distribution (left) and concentration (right). (b) qRT-PCR analysis of miR-34a level in LMVs, LMVsmiRCtrl, and LMVsmiR34a. Data represents mean ± SEM. ∗P < 0.05 versus LMVs; #P < 0.05 versus LMVsmiRCtrl. LMVs represent MVs generated from LSCs without transfection; LMVsmiRCtrl represent MVs generated from LSCs transfected with miRCtrl; and LMVsmiR34a represent MVs generated from LSCs transfected with miR34a mimic.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835649&req=5

fig2: The particle number and miR-34a level of LMVs, LMVsmiRCtrl, and LMVsmiR34a. (a) Representative NTA plots of MV size distribution (left) and concentration (right). (b) qRT-PCR analysis of miR-34a level in LMVs, LMVsmiRCtrl, and LMVsmiR34a. Data represents mean ± SEM. ∗P < 0.05 versus LMVs; #P < 0.05 versus LMVsmiRCtrl. LMVs represent MVs generated from LSCs without transfection; LMVsmiRCtrl represent MVs generated from LSCs transfected with miRCtrl; and LMVsmiR34a represent MVs generated from LSCs transfected with miR34a mimic.
Mentions: As shown in Figure 2(a), NTA analysis showed that the number of LMVsmiR34 was higher than that of LMVs or LMVsmiRCtrl, although there were no significant changes in their size distribution. More interestingly, the expression of miR34a in LMVs was displayed in the same pattern as their parent LSCs. As shown in Figure 2(a), qRT-PCR assay showed that the level of miR34a in LMVsmiR34 was much higher than that of LMVs or LMVsmiRCtrl. There was no significant difference of miR34a level between LMVs and LMVsmiRCtrl.

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