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Research article
hui cheng
Changhai Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9154-9282
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Acute myeloid leukemia (AML) is a malignancy commonly seen in adults. Previous studies indicated that TRIM14 played a tumorigenic role in various types of cancer and miR-23b-5p was down-regulated in human mesenchymal stem cell-derived exosomes (HMSC-exos) of AML patients. However, their roles in AML remains unclear. Our study aims to investigate the role of TRIM14 and miR-23b-5p in the pathogenesis of AML.
Materials and methods: The blood specimen was collected from AML patients and healthy donators. Exosomes were extracted from the culture medium of human mesenchymal stem cells under ultracentrifugation. Then exosomes were co-cultured with AML cells to determine the effect of their contents. The cell proliferation was detected by cell counting kit-8 assay, whereas the cell apoptosis was detected by flow cytometry. The expression of miR-23b-5p and TRIM14 was silenced or overexpressed to explore their biological functions in AML. Luciferase reporter assay was conducted to validate the interaction between miR-23b-5p and TRIM14. Gene expression was determined by quantitative real-time PCR and immunoblots.
Results: TRIM14 was significantly increased in AML patients and cell lines. The inhibition of TRIM14 significantly reduced the proliferation and induced the apoptosis of AML cells via activating PI3K/AKT pathway, whereas its overexpression exhibited reversed effects. HMSC-exos could suppress the proliferation of AML cells through the delivery of miR-23b-5p. Moreover, miR-23b-5p inhibited the transcription of TRIM14 by binding on its 3’UTR region. Overexpression of TRIM14 exhibited reversed effect against the function of miR-23b-5p mimic.
Conclusion: TRIM14 could promote the proliferation of AML cells via activating PI3K/AKT pathway, which was reversed by HMSC-exos through delivering miR-23b-5p. These findings indicated that miR-23b-5p and TRIM14 could be applied as potential targets for the treatment of AML.
Keywords
exosomes, human mesenchymal stem cell, acute myeloid leukemia, miR-23b-5p, TRIM14.
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This is a list of supplementary files associated with this preprint. Click to download.
- FigureS1.jpg
Figure S1. The inhibition and overexpression of TRIM14 in THP-1cells. A-B. The mRNA (A) and protein (B) levels of TRIM14 after transfecting with TRIM14 siRNAs in THP-1 cells. C-D. The mRNA (C) and protein (D) levels of TRIM14 after transfecting with TRIM14 overexpressed plasmid in HL-60 cells. *** p < 0.001.
- FigureS2.jpg
Figure S2. Identification of exosomes derived from HMSC. A. The positive (CD44 and CD90) and negative (CD34 and CD45) biomarkers for HMSC derived exosomes were detected by flow cytometry. B. Transmission electron microscopy revealed the morphology of HMSC-exos (scale bar = 100 nm). C. The expression of exosomal biomarkers (CD9, CD63 and CD81) in HMSC-exos.
- FigureS3.jpg
Figure S3. The expression of miR-23b-5p after the application of miR-23b-5p mimic and inhibitor. *** p < 0.001.
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This preprint is under consideration at Molecular Medicine. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
hui cheng
Changhai Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9154-9282
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 16 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 05 Apr, 2021
Reviewer #1 agreed
On 05 Apr, 2021
Editor assigned
On 09 Mar, 2021
Editor invited
On 09 Mar, 2021
Submission checks complete
On 09 Mar, 2021
First submitted
On 05 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Acute myeloid leukemia (AML) is a malignancy commonly seen in adults. Previous studies indicated that TRIM14 played a tumorigenic role in various types of cancer and miR-23b-5p was down-regulated in human mesenchymal stem cell-derived exosomes (HMSC-exos) of AML patients. However, their roles in AML remains unclear. Our study aims to investigate the role of TRIM14 and miR-23b-5p in the pathogenesis of AML.
Materials and methods: The blood specimen was collected from AML patients and healthy donators. Exosomes were extracted from the culture medium of human mesenchymal stem cells under ultracentrifugation. Then exosomes were co-cultured with AML cells to determine the effect of their contents. The cell proliferation was detected by cell counting kit-8 assay, whereas the cell apoptosis was detected by flow cytometry. The expression of miR-23b-5p and TRIM14 was silenced or overexpressed to explore their biological functions in AML. Luciferase reporter assay was conducted to validate the interaction between miR-23b-5p and TRIM14. Gene expression was determined by quantitative real-time PCR and immunoblots.
Results: TRIM14 was significantly increased in AML patients and cell lines. The inhibition of TRIM14 significantly reduced the proliferation and induced the apoptosis of AML cells via activating PI3K/AKT pathway, whereas its overexpression exhibited reversed effects. HMSC-exos could suppress the proliferation of AML cells through the delivery of miR-23b-5p. Moreover, miR-23b-5p inhibited the transcription of TRIM14 by binding on its 3’UTR region. Overexpression of TRIM14 exhibited reversed effect against the function of miR-23b-5p mimic.
Conclusion: TRIM14 could promote the proliferation of AML cells via activating PI3K/AKT pathway, which was reversed by HMSC-exos through delivering miR-23b-5p. These findings indicated that miR-23b-5p and TRIM14 could be applied as potential targets for the treatment of AML.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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