Blood Res.  2023 Sep;58(3):133-137. 10.5045/br.2023.2023097.

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

• Kang SH
• Choi JS

• KMID: 2546314
• DOI: http://doi.org/10.5045/br.2023.2023097

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.

Keyword

MDS; microRNA; Deregulation; Apoptosis; Pathogenesis

Figure

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  Fig. 1 Relative expression of miR-765 in patients (A) with MDS and controls and (B) with and without trisomy 1q.

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  Fig. 2 Cell proliferation after transfection with a miR-765 mimic (miR-765) or a negative control miRNA.

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  Fig. 3 (A, B) Annexin V (FITC)/PI assay and (C) caspase assay after transfection with a negative control miRNA (NC) and miR-765 mimic.

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  Fig. 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).

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