Effect of U2AF1 Mutation to Inflammatory Cytokine Expression in SKM-1 Cells through FOXO3a-Bim Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of U2AF1 gene mutation to inflammatory cytokine in SKM-1 cell of human myelodysplastic syndromes (MDS), and whether the above effects were mediated by FOXO3a-Bim signaling pathway.@*METHODS@#Wide-type U2AF1 and mutant U2AF1 (the serine residue 34 was replaced by phenylalanine, and named as S34F) recombinant expression plasmids were constructed. Lentiviruses were packaged and transfected into SKM-1 cells. The expression of FOXO3a was up-regulated by lentiviruses, and its transfection rate was investigated. The cell proliferation was detected by CCK-8 method. Flow cytometry was used to detect the apoptosis and cycle of the cells. The expression pro-inflammatory cytokine IL-1β, IL-6, TNF-α and anti-inflammatory cytokine IL-4 were detected by qRT-PCR. FOXO3a, Bim, Bcl-2 and Bax protein expression levels were detected by Western blot.@*RESULTS@#Compared with the control group, the cell apoptosis rate, pro-inflammatory cytokine IL-1β and TNF-α transcription levels were significantly increased in the S34F group (P<0.05); cell cycle was blocked at the G@*CONCLUSION@#U2AF1 S34F mutation can regulate inflammatory phenotype in SKM-1 cells, which may be mediated through FOXO3a-Bim signaling pathway.

Research advances in role of m6A methylation modification in hematological malignancies / 上海交通大学学报（医学版）

N6-methyladenosine (m6A) has been identified as the most common epigenetic modification of eukaryote mRNA. It can not only mediate multiple processes of RNA metabolism such as RNA splicing, translation and decay under the catalytic regulation of m6A-related enzymes, but also affect the development of bone marrow hematopoiesis by regulating the self-renewal, proliferation and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, many studies have reported that m6A methylation modification plays an important role in the development and progression of hematological malignancies. Targeting inhibition of m6A-related factors contributes to increase the sensitivity of patients with hematological malignancies to therapeutic drugs. This review describes the biological characteristics and hematopoietic regulation mechanisms of m6A methylation modification, and its role in the pathogenesis of hematological malignancies.