Original Article

Split Viewer

Blood Res 2023; 58(3):

Published online September 30, 2023

https://doi.org/10.5045/br.2023.2023097

© The Korean Society of Hematology

MicroRNA-765 is upregulated in myelodysplastic syndromes and induces apoptosis via PLP2 inhibition in leukemia cells

Seong-Ho Kang1, Ji Seon Choi2

Department of Laboratory Medicine, 1Chosun University College of Medicine, Gwangju, 2International St. Mary’s Hospital, Catholic Kwandong University, Incheon, Korea

Correspondence to : Seong-Ho Kang, M.D., Ph.D.
Department of Laboratory Medicine, Chosun University College of Medicine, 365 Pilmun-daero, Dong-gu, Gwangju 61453, Korea
E-mail: seonghomed@hanmail.net

*This study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2021R1F1A1045955).

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Correction: Blood Research (2024) 59:20

Background
Epigenetic studies, particularly research on microRNA (miRNA), have flourished. The abnormal expression of miRNA contributes to the development of hematologic malignancies. miR-765 has been reported to inhibit cell proliferation by downregulating proteolipid protein 2 (PLP2), which causes apoptosis. We investigated miR-765 dysregulation in myelodysplastic syndromes (MDS).
Methods
We compared the expression profiles of miR-765 in 65 patients with MDS and 11 controls. Cell proliferation and apoptosis assays were performed to determine the in vitro effects of miR-765 on leukemia cells transfected with the miR-765 mimic. Reverse transcription quantitative PCR (RT-qPCR) and western blotting were performed to examine the targets of miR-765.
Results
We found that miR-765 levels were upregulated 10.2-fold in patients with MDS compared to controls. In refractory cytopenia with multilineage dysplasia, the percentage of patients with elevated miR-765 levels was significantly higher than in other forms of MDS. Experiments with leukemia cells revealed that transfection with a miR-765 mimic inhibited cell proliferation and induced apoptosis. RT-qPCR and western blotting demonstrated that the target of miR-765 was PLP2.
Conclusion
These findings imply that upregulation of miR-765 induces apoptosis via downregulation of PLP2 and may have a role in MDS pathogenesis.


Keywords: MDS, microRNA, Deregulation, Apoptosis, Pathogenesis

Article

Original Article

Blood Res 2023; 58(3): 133-137

Published online September 30, 2023 https://doi.org/10.5045/br.2023.2023097

Copyright © The Korean Society of Hematology.

MicroRNA-765 is upregulated in myelodysplastic syndromes and induces apoptosis via PLP2 inhibition in leukemia cells

Seong-Ho Kang1, Ji Seon Choi2

Department of Laboratory Medicine, 1Chosun University College of Medicine, Gwangju, 2International St. Mary’s Hospital, Catholic Kwandong University, Incheon, Korea

Correspondence to:Seong-Ho Kang, M.D., Ph.D.
Department of Laboratory Medicine, Chosun University College of Medicine, 365 Pilmun-daero, Dong-gu, Gwangju 61453, Korea
E-mail: seonghomed@hanmail.net

*This study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2021R1F1A1045955).

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Correction: Blood Research (2024) 59:20

Abstract

Background
Epigenetic studies, particularly research on microRNA (miRNA), have flourished. The abnormal expression of miRNA contributes to the development of hematologic malignancies. miR-765 has been reported to inhibit cell proliferation by downregulating proteolipid protein 2 (PLP2), which causes apoptosis. We investigated miR-765 dysregulation in myelodysplastic syndromes (MDS).
Methods
We compared the expression profiles of miR-765 in 65 patients with MDS and 11 controls. Cell proliferation and apoptosis assays were performed to determine the in vitro effects of miR-765 on leukemia cells transfected with the miR-765 mimic. Reverse transcription quantitative PCR (RT-qPCR) and western blotting were performed to examine the targets of miR-765.
Results
We found that miR-765 levels were upregulated 10.2-fold in patients with MDS compared to controls. In refractory cytopenia with multilineage dysplasia, the percentage of patients with elevated miR-765 levels was significantly higher than in other forms of MDS. Experiments with leukemia cells revealed that transfection with a miR-765 mimic inhibited cell proliferation and induced apoptosis. RT-qPCR and western blotting demonstrated that the target of miR-765 was PLP2.
Conclusion
These findings imply that upregulation of miR-765 induces apoptosis via downregulation of PLP2 and may have a role in MDS pathogenesis.

Keywords: MDS, microRNA, Deregulation, Apoptosis, Pathogenesis

Fig 1.

Figure 1.Relative expression of miR-765 in patients (A) with MDS and controls and (B) with and without trisomy 1q.
Blood Research 2023; 58: 133-137https://doi.org/10.5045/br.2023.2023097

Fig 2.

Figure 2.Cell proliferation after transfection with a miR-765 mimic (miR-765) or a negative control miRNA.
Blood Research 2023; 58: 133-137https://doi.org/10.5045/br.2023.2023097

Fig 3.

Figure 3.(A, B) Annexin V (FITC)/PI assay and (C) caspase assay after transfection with a negative control miRNA (NC) and miR-765 mimic.
Blood Research 2023; 58: 133-137https://doi.org/10.5045/br.2023.2023097

Fig 4.

Figure 4.(A) mRNA analysis of PLP2 and (B) western blot analysis after transfection with a miR-765 mimic (miR-765) or negative control miRNA (NC).
Blood Research 2023; 58: 133-137https://doi.org/10.5045/br.2023.2023097

Patients distribution according to miR-765 expression and MDS subtypes..


MDS subtypesN of patients (%)
Low miR-765 expressionHigh miR-765 expression
RCUD7 (21.9%)2 (6.1%)
RARS0 (0%)1 (3.0%)
RCMD8 (25%)19 (57.6%)
RAEB-15 (16.7%)4 (12.1%)
RAEB-24 (12.5%)6 (1.1%)
MDS U8 (25%)1 (3.0%)
Total32 (100%)33 (100%)

Abbreviations: MDS, myelodysplastic syndromes; MDS U, unclassified myelodysplastic syndromes; RAEB-1, refractory anemia with excess blasts type 1; RAEB-2, refractory anemia with excess blasts type 2; RARS, refractory anemia with ring sideroblasts; RCUD, refractory cytopenia with unilineage dysplasia..



Patients distribution according to miR-765 expression and IPSS-R subgroups..


Prognostic subgroupsN of patients (%)
Low miR-765 expressionHigh miR-765 expression
Very low2 (6.7%)2 (6.7%)
Low4 (13.3%)6 (16.7%)
Intermediate12 (40.0%)10 (33.3%)
High5 (16.7%)4 (13.3%)
Very high7 (23.3%)5 (16.7%)
Total30 (100%)30 (100%)

Abbreviation: IPSS-R, International Prognostic Scoring System..


Blood Res
Volume 59 2024

Stats or Metrics

Share this article on

  • line

Related articles in BR

Blood Research

pISSN 2287-979X
eISSN 2288-0011
qr-code Download