A possible role for microRNA765 (miR-765) in the pathogenesis of myelodysplastic syndromes (MDS) has been suggested, according to findings from a study conducted in Korea and published in the journal Blood Research.
It is well known that the abnormal expression of miRNA is associated with the development of hematologic malignancies such as MDS. It has been reported that miR-765 is responsible for inhibition of cell proliferation via downregulation of proteolipid protein 2 (PLP2), which, in turn, leads to apoptosis. Patients with MDS have a high risk for progression to acute myeloid leukemia (AML).
“miRNAs are short, non-coding RNAs that are critical regulators of hematopoiesis.” The researchers of the current analysis sought to evaluate the association of miR-765 with MDS. They compared the expression of miR-675 among patients with MDS and controls, along with the in vitro effect of miR-765 on hematopoietic cells via use of an AML cell line that had been transfected with a mimic of miR-765. The targets of miR-765 were examined via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis.
Sixty-five patients with MDS and 11 healthy controls participated in the study. None of the controls exhibited evidence of cancer or normocellular bone marrow and had no indication of any hematologic malignancies. Study participants comprised the following groups of patients with MDS:
- 9 individuals with refractory cytopenia with unilineage dysplasia
- 1 participant with refractory anemia with ring sideroblasts
- 27 patients with refractory cytopenia with multilineage dysplasia
- 9 individuals with refractory anemia of excess blasts type 1
- 10 participants with refractory anemia of excess blasts type 2
- 9 patients with unclassifiable MDS
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Study results showed that miR-765 expression among the patients was significantly higher than the expression in the controls (P =.0019), thus indicating that miR-765 expression levels were upregulated 10.2-fold in the participants with MDS compared with miR-765 concentrations in the controls.
Among those with refractory cytopenia with multilineage dysplasia, the proportion of patients with elevated miR-675 levels was significantly higher than that among those with other forms of MDS (P =.0014)
Based on in vitro experiments that were performed with human AML cells (ie, OCI-AML3), when the cells were transfected with an miR-765 mimic or a negative control miRNA via a cell proliferation assay, cell growth was shown to be significantly inhibited after transfection with miR-675 compared with the negative control (P <.0001). According to the results of RT-qPCR and Western blot analyses, the target of miR-675 was PLP2.
“These findings imply that upregulation of miR-675 induces apoptosis via downregulation of PLP2 and may have a role in MDS pathogenesis,” the researchers noted. “Further studies on PLP2 in MDS are required to elucidate its pathophysiological role,” they concluded.
Reference
Kang S-H, Choi JS. MicroRNA-765 is upregulated in myelodysplastic syndromes and induces apoptosis via PLP2 inhibition in leukemia cells. Blood Res. Published online July 27, 2023. doi:10.5045/br.2023.2023097
