The promoter of MEG3, which encodes the long non-coding RNA (lncRNA) MEG3, is often hypermethylated in acute myeloid leukemia (AML). Additionally, the Tet methylcytosine dioxygenase 2 gene (TET2) is frequently inactivated, which can lead to impaired DNA methylation and promote AML development. We examined the association between TET2 and MEG3 promoter hypermethylation in Hainan patients with AML. The expression of MEG3, TET2, miR-22-3p, and miR-22-5p was assessed in bone marrow samples from AML patients and healthy controls using real-time quantitative PCR. Using Sequenom MassARRAY technology, we compared MEG3 promoter methylation in AML patients and healthy controls. MEG3 expression was lower in AML patients than in the controls (P = 0.136). Moreover, there was greater methylation of MEG3 promoter in the AML patients than the controls (P < 0.05). Methylation of the MEG3 promoter correlated negatively with TET2 expression (P < 0.05, r < 0). Likewise there was a negative correlation between TET2 activity and MEG3 promoter methylation (P < 0.05, r < 0). These results suggest that hypermethylation of the MEG3 promoter in AML may result from decreased TET2 activity. These data provide insight into the molecular mechanisms underlying AML development and progression.

AimAcute myeloid leukemia (AML) is the most common blood tumor with poor prognosis. At present, the research found that the pathogenesis of AML is related to many factors, such as recurrent somatic mutations and gene expression and epigenetic changes, however, the molecular mechanism of AML is still unclear. Long non-coding RNA MEG3 is a newly found tumor suppressor and plays a very important role in the regulation of a variety of tumor formation and progression. Studies found that the MEG3 expression was significantly decreased in AML. However, to date, it is not clear the cause of its abnormal expression. Therefore, the molecular mechanism of AML is urgently needed to study the molecular mechanism of AML.MethodsThe different expression level of MEG3, TET2, miR-22-3p, miR-22-5p in AML was detected by real-time quantification PCR. MEG3, TET2, miR-22-3p, miR-22-3p expression cell pools in K562 cells was used to interfering and TET2, MEG3 TET2, relations with miR-22-3p, miR-22-5p. The effect of AML cell on proliferation was evaluated by TET2 lower expression.Results1. The lower expression of MEG3 and TET2 in AML cell lines was detected by RT-qPCR. 2. The stable MEG3, TET2 overexpression cell pools in K562 cells was successful established. 3. After transfection, MTT assay revealed that cell growth was significantly increased in AML cell lines transfected with TET2 compared with controls.ConclusionsOur findings suggested that MEG3 is significantly down regulated in AML cell lines.

PurposeChronic obstructive pulmonary disease (COPD) is a major and an increasingly prevalent health problem worldwide. It has been reported that genetic variation may play a role in the development and severity of COPD. The purpose of this study was to investigate whether single nucleotide polymorphisms in multiple genetic variants were associated with COPD in a Chinese population from Hainan province.MethodsIn this case-control study, including 200 COPD patients and 401 controls, we genotyped 14 tag single nucleotide polymorphisms and evaluated their association with COPD using the χ2 test and genetic model analysis.ResultsThe polymorphism, rs10007052, in the RNF150 gene was significantly associated with COPD risk at a 5% level (odds ratio =1.43, 95% confidence interval, 1.06–1.95, P=0.020). In the log-additive model, the minor allele (C) of rs10007052 in the RNF150 gene (P=0.026) and the minor allele (C) of rs3733829 in the EGLN2 gene (P=0.037) were associated with COPD risk after adjustment for age, sex, and smoking status. Further haplotype analysis revealed that the “CT” haplotype composed of the mutant allele (C) of rs7937, rs3733829 in the EGLN2 gene, was associated with increased COPD risk (odds ratio =1.55; 95% confidence interval, 1.05–2.31; P=0.029).ConclusionOur findings indicated that rs10007052 in the RNF150 and rs3733829 in the EGLN2 gene were significantly associated with the risk of COPD in Chinese populations of Hainan province. These data may provide novel insights into the pathogenesis of COPD, although further studies with larger numbers of participants worldwide are needed for validation of our conclusions.

Rituximab is a mouse and human chimeric CD 20 (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD 20 antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD 20 molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.

BackgroundChronic myeloid leukemia (CML) is a major global health threat due to its low cure rate and high fatality rate. Studies have reported that miR-22, TET2, and p53 play a vital role in the progression of leukemia. However, it is unclear whether there is feedback regulation between them.MethodsTransfection efficiency of miR-22 and TET2 was detected by qRT-PCR. CCK-8 assay was applied to measure the proliferation ability of K562 cells. Flow cytometry was used for evaluation the cell cycle and apoptosis rate of K562 cells after transfection. Moreover, the interaction between miR-22, TET2 and P53 was analyzed by luciferase reporter gene assay.ResultsExperiments indicated that the TET2 expression was decreased and apoptosis was increased in the miR-22 mimic group, and cell cycle was arrested in G0/G1phase, the proliferation was markedly inhibited. Meanwhile we found that TET2 can affect the expression of p53. Then, we directly proved p53 inhibition miR-22 transcription, whereas miR-22 as a transcriptional repressor, TET2 expression is negatively regulated to form a feedback loop.ConclusionsmiR-22, TET2 and p53 can form a feedback loop and thus affect cell proliferation and apoptosis of chronic myeloid leukemia cells.