Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway

Chen Zhao; Yang Zhao; Jiaqi Zhao; Guixian Meng; Shuyu Huang; Yichen Liu; Shanshan Wang; Ling Qi

doi:10.1038/s41417-021-00378-6

Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway

Chen Zhao, Yang Zhao, Jiaqi Zhao, Guixian Meng, Shuyu Huang, Yichen Liu, Shanshan Wang, Ling Qi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

microRNAs (miRNAs or miRs) can be delivered from acute myeloid leukemia (AML) cells to hematopoietic stem cells (HSCs) to regulate hematopoietic function via extracellular vesicles (EVs). In this study, we investigated the roles played by EVs that transport miR-548ac from AML cells in normal hematopoiesis. Bioinformatics analysis demonstrated that miR-548ac was highly expressed in AML-derived EVs. The expression of miR-548ac and TRIM28 and the targeting relationship were identified, and the results demonstrated that the expression of miR-548ac was upregulated in AML cell lines and AML cell-secreted EVs compared with CD34⁺ HSCs. AML-derived EVs targeted CD34⁺ HSCs to induce decreased expression of TRIM28 and downstream activation of STAT3. Exosomal miR-548ac was transferred into CD34⁺ HSCs to target TRIM28. Through gain- and loss-of-function assays, it was observed that the abrogated expression of miR-548ac or STAT3 promoted colony-forming units (CFU), whereas overexpressed miR-548ac repressed CFU, which was rescued by overexpression of TRIM28. Taken together, these results indicated that miR-548ac delivered by AML cell-derived EVs inhibits hematopoiesis via TRIM28-dependent STAT3 activation.

Original language	English
Pages (from-to)	918-929
Number of pages	12
Journal	Cancer Gene Therapy
Volume	29
Issue number	7
DOIs	https://doi.org/10.1038/s41417-021-00378-6
Publication status	Published - Jul 2022
Externally published	Yes

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title = "Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway",

abstract = "microRNAs (miRNAs or miRs) can be delivered from acute myeloid leukemia (AML) cells to hematopoietic stem cells (HSCs) to regulate hematopoietic function via extracellular vesicles (EVs). In this study, we investigated the roles played by EVs that transport miR-548ac from AML cells in normal hematopoiesis. Bioinformatics analysis demonstrated that miR-548ac was highly expressed in AML-derived EVs. The expression of miR-548ac and TRIM28 and the targeting relationship were identified, and the results demonstrated that the expression of miR-548ac was upregulated in AML cell lines and AML cell-secreted EVs compared with CD34+ HSCs. AML-derived EVs targeted CD34+ HSCs to induce decreased expression of TRIM28 and downstream activation of STAT3. Exosomal miR-548ac was transferred into CD34+ HSCs to target TRIM28. Through gain- and loss-of-function assays, it was observed that the abrogated expression of miR-548ac or STAT3 promoted colony-forming units (CFU), whereas overexpressed miR-548ac repressed CFU, which was rescued by overexpression of TRIM28. Taken together, these results indicated that miR-548ac delivered by AML cell-derived EVs inhibits hematopoiesis via TRIM28-dependent STAT3 activation.",

author = "Chen Zhao and Yang Zhao and Jiaqi Zhao and Guixian Meng and Shuyu Huang and Yichen Liu and Shanshan Wang and Ling Qi",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

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doi = "10.1038/s41417-021-00378-6",

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T1 - Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway

AU - Zhao, Chen

AU - Zhao, Yang

AU - Zhao, Jiaqi

AU - Meng, Guixian

AU - Huang, Shuyu

AU - Liu, Yichen

AU - Wang, Shanshan

AU - Qi, Ling

PY - 2022/7

Y1 - 2022/7

N2 - microRNAs (miRNAs or miRs) can be delivered from acute myeloid leukemia (AML) cells to hematopoietic stem cells (HSCs) to regulate hematopoietic function via extracellular vesicles (EVs). In this study, we investigated the roles played by EVs that transport miR-548ac from AML cells in normal hematopoiesis. Bioinformatics analysis demonstrated that miR-548ac was highly expressed in AML-derived EVs. The expression of miR-548ac and TRIM28 and the targeting relationship were identified, and the results demonstrated that the expression of miR-548ac was upregulated in AML cell lines and AML cell-secreted EVs compared with CD34+ HSCs. AML-derived EVs targeted CD34+ HSCs to induce decreased expression of TRIM28 and downstream activation of STAT3. Exosomal miR-548ac was transferred into CD34+ HSCs to target TRIM28. Through gain- and loss-of-function assays, it was observed that the abrogated expression of miR-548ac or STAT3 promoted colony-forming units (CFU), whereas overexpressed miR-548ac repressed CFU, which was rescued by overexpression of TRIM28. Taken together, these results indicated that miR-548ac delivered by AML cell-derived EVs inhibits hematopoiesis via TRIM28-dependent STAT3 activation.

AB - microRNAs (miRNAs or miRs) can be delivered from acute myeloid leukemia (AML) cells to hematopoietic stem cells (HSCs) to regulate hematopoietic function via extracellular vesicles (EVs). In this study, we investigated the roles played by EVs that transport miR-548ac from AML cells in normal hematopoiesis. Bioinformatics analysis demonstrated that miR-548ac was highly expressed in AML-derived EVs. The expression of miR-548ac and TRIM28 and the targeting relationship were identified, and the results demonstrated that the expression of miR-548ac was upregulated in AML cell lines and AML cell-secreted EVs compared with CD34+ HSCs. AML-derived EVs targeted CD34+ HSCs to induce decreased expression of TRIM28 and downstream activation of STAT3. Exosomal miR-548ac was transferred into CD34+ HSCs to target TRIM28. Through gain- and loss-of-function assays, it was observed that the abrogated expression of miR-548ac or STAT3 promoted colony-forming units (CFU), whereas overexpressed miR-548ac repressed CFU, which was rescued by overexpression of TRIM28. Taken together, these results indicated that miR-548ac delivered by AML cell-derived EVs inhibits hematopoiesis via TRIM28-dependent STAT3 activation.

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Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway

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