Down-regulation of Notch-1 expression decreases PU.1-mediated myeloid differentiation signaling in acute myeloid leukemia

miRNA has always been a hot spot research. We assessed the effect of down-regulation of miR-23b-3p on the differentiation of acute myeloid leukemia (AML). Human AML cell line U937 was divided into blank group, NC group and miR-23b-3p low expression group (transfected with miR-23b-3p inhibitor) and miR-23b-3p followed by analysis of WT1 level and relationship between miR-23b-3p and WT1 by dual luciferase reporter assay. All-trans retinoic acid is used to induce differentiation, and then the morphological changes of cells and CD11b level were detected. When miR-23b-3p level was reduced, WT1 mRNA and protein level was also decreased. Dual luciferase assay showed that miR-23b-3p bound to WT1 3’-UTR. Inhibition of miR-23b-3p significantly decreased cell proliferation. Swiss Giemsa staining showed that most of cells were in the differentiation stage with low miR-23b-3p expression. The differentiation marker CD11b was significantly higher than other groups, indicating that low miR-23b-3p expression can promote cell differentiation and reduce cell proliferation to a certain extent. Under low miR-23b-3p expression, the positive rate of CD11b was significantly increased. Down-regulating miR-23b-3p can inhibit WT1 to a certain extent and promote the differentiation of AML, which provides a guidance for the gene-level treatment of AML.

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The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis

Scientific Reports ◽

10.1038/srep24589 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 13

Author(s):

Xuejing Shao ◽

Yujia Liu ◽

Yangling Li ◽

Miao Xian ◽

Qian Zhou ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Retinoic Acid ◽

Myeloid Leukemia ◽

Leukemia Cells ◽

Myeloid Differentiation ◽

Human Acute Myeloid Leukemia ◽

Acute Myeloid Leukemia Cells ◽

Acute Myeloid

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Silencing long non-coding RNA XIST suppresses drug resistance in acute myeloid leukemia through down-regulation of MYC by elevating microRNA-29a expression

Molecular Medicine ◽

10.1186/s10020-020-00229-4 ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Chong Wang ◽

Lingling Li ◽

Mengya Li ◽

Weiqiong Wang ◽

Yanfang Liu ◽

...

Keyword(s):

Bone Marrow ◽

Drug Resistance ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Cellular Viability ◽

Down Regulation ◽

Acute Myeloid

Abstract Background Long non-coding RNAs (lncRNAs) are biomarkers participating in multiple disease development including acute myeloid leukemia (AML). Here, we investigated molecular mechanism of X Inactive-Specific Transcript (XIST) in regulating cellular viability, apoptosis and drug resistance in AML. Methods XIST, miR-29a and myelocytomatosis oncogene (MYC) expression in AML bone marrow cells collected from 62 patients was evaluated by RT-qPCR and Western blot analysis. Besides, the relationship among XIST, miR-29a and MYC was analyzed by dual luciferase reporter assay, RIP, and RNA pull down assays. AML KG-1 cells were treated with anti-tumor drug Adriamycin. The role of XIST/miR-29a/MYC in cellular viability, apoptosis and drug resistance in AML was accessed via gain- and loss-of-function approaches. At last, we evaluated role of XIST/miR-29a/MYC on tumorigenesis in vivo. Results XIST and MYC were up-regulated, and miR-29a was down-regulated in AML bone marrow cells. Silencing XIST inhibited cellular activity and drug resistance but promoted cellular apoptosis of KG-1 cells by down-regulating MYC. XIST inhibited miR-29a expression to up-regulate MYC. Moreover, silencing XIST inhibited tumorigenesis of AML cells in vivo. Conclusions Overall, down-regulation of XIST decreased MYC expression through releasing the inhibition on miR-29a, thereby reducing drug resistance, inhibiting viability and promoting apoptosis of AML cells.

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