Relationship of miRNA-181b and prognostic factors of myelodysplastic syndrome and the prediction of target genes / 白血病·淋巴瘤

ABSTRACT

Objective:To investigate the correlation of miRNA-181b (miR-181b) and prognostic factors of myelodysplastic syndrome (MDS), to predict target gene and main biological functions of miR-181b, and to evaluate the risk prediction ability of miR-181b in MDS.Methods:The samples of 131 bone marrow in MDS patients who followed the criteria of World Health Organization (WHO) classification (2016) from the Blood Diseases Hospital, Chinese Academy of Medical Sciences between January 2019 and September 2019 were collected, and the clinical data including routine blood test results, related gene test results of blood diseases were retrospectively analyzed. The expression levels of miR-181b in all bone marrow samples were detected by using quantitative real-time polymerase chain reaction (qRT-PCR). According to the international prognostic scoring system (IPSS), WHO classification-based prognostic scoring system (WPSS) and revised IPSS (IPSS-R), the patients were divided into different groups by the risk grade, and the expression differences of miR-181b in different risk groups were compared, and the correlation between the expressions of miR-181b and partial prognostic factors, including white blood cell (WBC), hemoglobin (Hb), platelet (Plt), absolute neutrophil count(ANC), myeloblast and gene mutations was analyzed. Bioinformatics online tool TargetScan was used to make target gene prediction and the potential function of miR-181b.Results:The expression levels of miR-181b was increased with the increasing risk of IPSS, WPSS and IPSS-R, and there were statistically significant differences in miR-181b expression levels of different risk groups in different scoring systems (all P < 0.01). There was a positive correlation between the expression level of miR-181b and the scores of the three prognostic scoring systems (r was 0.437, 0.368, 0.327; all P = 0.001); miR-181b expression was positively correlated with the proportion of bone marrow myeloblasts ( r = 0.450, P < 0.01) and was negatively correlated with Plt ( r = -0.199, P = 0.024). And miR-18b was not associated with WBC, Hb, ANC, and related gene mutations of blood diseases (all P > 0.05). A total of 1 363 potential target genes of miR-181b were predicted by using bioinformatics, and biological processes of these target genes were mainly enriched in transcription regulation, RNA metabolism regulation. Among them, 22 target genes were related to the hematological malignancies, including RUNX1, ASXL2, NRAS, ATM and KRAS, which have been previously confirmed to be related to MDS. The relative expression level [the median ( P25, P75)] of miR-181b in patients who had those hematological malignancies related to miR-181b target gene mutation (32 cases) was 1.33(0.63, 1.60), which was higher than that in patients without mutation (99 cases) [0.85 (0.49, 1.38)], and the difference was statistically significant ( Z = 2.285, P = 0.022). Conclusions:miR-181b has a correlation with the risk grade of prognostic scoring systems in MDS, and it may be involved in the molecular biology pathogenesis of MDS.