SPRY1 promotes cell proliferation and inhibits apoptosis by activating Hedgehog pathway 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 small-molecule compound AC-73 targeting CD147 inhibits leukemic cell proliferation, induces autophagy and increases the chemotherapeutic sensitivity of acute myeloid leukemia cells

Haematologica ◽

10.3324/haematol.2018.199661 ◽

2018 ◽

Vol 104 (5) ◽

pp. 973-985 ◽

Cited By ~ 8

Author(s):

Isabella Spinello ◽

Ernestina Saulle ◽

Maria Teresa Quaranta ◽

Luca Pasquini ◽

Elvira Pelosi ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Myeloid Leukemia ◽

Small Molecule ◽

Myeloid Leukemia ◽

Leukemic Cell ◽

Leukemia Cells ◽

Chemotherapeutic Sensitivity ◽

Acute Myeloid Leukemia Cells ◽

Small Molecule Compound ◽

Acute Myeloid

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Knockdown of Long Noncoding RNA HOXA-AS2 Suppresses Chemoresistance of Acute Myeloid Leukemia via the miR-520c-3p/S100A4 Axis

Cellular Physiology and Biochemistry ◽

10.1159/000495387 ◽

2018 ◽

Vol 51 (2) ◽

pp. 886-896 ◽

Cited By ~ 26

Author(s):

Xiaoya Dong ◽

Zhigang Fang ◽

Mingxue Yu ◽

Ling Zhang ◽

Ruozhi Xiao ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Reporter Assay ◽

Online Programs ◽

Acute Myeloid

Background/Aims: Among different molecular candidates, there is growing data to support that long noncoding RNAs (lncRNAs) play a significant role in acute myeloid leukemia (AML). HOXA-AS2 is significantly overexpressed in a variety of tumors and associated with anti-cancer drug resistance, however, little is known regarding the expression and function of HOXA-AS2 in the chemoresistance of AML. In this study, we aimed to determine the role and molecular mechanism of HOXA-AS2 in adriamycin-based chemotherapy resistance in AML cells. Methods: Quantitative real-time PCR was used to detect HOXA-AS2 expression in the BM samples and ADR cell lines, U/A and T/A cells. Furthermore, the effects of HOXA-AS2 silencing on cell proliferation and apoptosis were assessed in vitro by CCK8 and flow cytometry, and on tumor growth in vivo. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in AML. Results: In this study, we showed that HOXA-AS2 is significantly upregulated in BM samples from AML patients after treatment with adriamycin-based chemotherapy and in U/A and T/A cells. Knockdown of HOXA-AS2 inhibited ADR cell proliferation in vitro and in vivo and promoted apoptosis. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3’-UTR with complementary binding sites, which was validated using luciferase reporter assay and anti-Ago2 RIP assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in ADR cells. S100A4 was predicted as a downstream target of miR-520c-3p, which was confirmed by luciferase reporter assay. Conclusion: Our results suggest that HOXA-AS2 plays an important role in the resistance of AML cells to adriamycin. Thus, HOXA-AS2 may represent a therapeutic target for overcoming resistance to adriamycin-based chemotherapy in AML.

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