CHD4 orchestrates the symphony of T and B lymphocytes development and a good mediator in preventing from autoimmune disease.

Chromodomain helicase DNA binding protein 4 (CHD4) is an ATPase subunit of the nucleosome remodeling and deacetylation complex. It has been implicated in gene transcription, DNA damage repair, maintenance of genome stability, and chromatin assembly. Meanwhile, it is highly related to cell cycle progression and the proceeding of malignancy. Most of the previous studies were focused on the function of CHD4 with tumor cells, cancer stem cells, and cancer cells multidrug resistance. Recently, some researchers have explored the CHD4 functions on the development and differentiation of adaptive immune cells, such as T and B lymphocytes. In this review, we will discuss details of CHD4 in lymphocyte differentiation and development, as well as the critical role of CHD4 in the pathogenesis of the autoimmune disease.

CircMYC regulates the mitochondrial respiration and cell viability via miR-516a-5p/AKT3 axis in acute myeloid leukemia.

OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy with an aberrant proliferation of immature myeloid cells. This study aimed at exploring the regulatory function of circMYC in AML progression. METHODS: Expression levels of CircMYC, miR-516a-5p, AKT3 and apoptosis-related proteins were determined by RT-qPCR and western blot. Cell viability and proliferation were examined by CCK8 assay and EdU assay. Annexin V/PI staining was used to assess cell apoptosis. Mitochondrial respiration function was confirmed by oxygen consumption rate (OCR). The relationships among circMYC, miR-516a-5p and AKT3 were detected by dual-luciferase reporter (DLR) assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay, respectively. RESULTS: CircMYC was positively correlated with poor prognosis in AML patients (all P<0.05). Knockdown of circMYC decreased cell viability and OCR but increased cell apoptosis rates (all P<0.05), and miR-516a-5p overexpression displayed the similar trend. Mechanistically, the oncogenic effects of circMYC were achieved by sponging miR-516a-5p and increasing AKT3. CONCLUSION: Decreased expression of circMYC could suppress AML progression by regulating miR-516a-5p/AKT3, suggesting a new therapeutic target in AML treatment.

Double Insurance for OC: miRNA-Mediated Platinum Resistance and Immune Escape.

Ovarian cancer (OC) is still the leading cause of death among all gynecological malignancies, despite the recent progress in cancer therapy. Immune escape and drug resistance, especially platinum-based chemotherapy, are significant factors causing disease progression, recurrence and poor prognosis in OC patients. MicroRNAs(miRNAs) are small noncoding RNAs, regulating gene expression at the transcriptional level. Accumulating evidence have indicated their crucial roles in platinum resistance. Importantly, they also act as mediators of tumor immune escape/evasion. In this review, we summarize the recent study of miRNAs involved in platinum resistance of OC and systematically analyses miRNAs involved in the regulation of OC immune escape. Further understanding of miRNAs roles and their possible mechanisms in platinum resistance and tumor escape may open new avenues for improving OC therapy.

Potential efficacy and prognosis of silencing the CRLF2­mediated AKT/mTOR pathway in pediatric acute B­cell lymphoblastic leukemia.

Acute B­cell lymphoblastic leukemia (B­ALL) is a common type of blood cancer, which is associated with aberrant gene expression. Cytokine receptor­like factor 2 (CRLF2) serves a crucial role in the growth and allergic and inflammatory responses of dendritic cells and T cells. The purpose of the present study was to investigate the potential therapeutic and prognostic effect of silencing the CRLF2­mediated RAC­α serine/threonine­protein kinase (AKT)/serine/threonine­protein kinase mTOR (mTOR) pathway in B­ALL. In our study, bone marrow specimens were collected from 128 children with B­ALL and 26 healthy children. The expression of CRLF2 in bone marrow tissue was detected using immunohistochemistry. The survival rates were compared among the children with high and low CRLF2 expression levels. BaF3 leukemia cells were treated with CRLF2 short hairpin RNA knockdown and/or the AKT/mTOR pathway specific inhibitor LY294002. mRNA and protein expression associated with CRLF2 and the AKT/mTOR pathway in each group was detected by reverse transcription­quantitative polymerase chain reaction analysis and western blotting. The viability of BaF3 cells in all the groups was assessed by Cell Counting Kit­8 assay; the migration and invasion of BaF3 cells were determined by wound healing and Transwell invasion assays; and the sensitivity of BaF3 cells to the chemotherapeutic drug imatinib was detected using flow cytometry. The results demonstrated that CRLF2 overexpression is associated with a poor prognosis in B­ALL, and the CRLF2/AKT/mTOR pathway is involved in the migration, invasion and chemotherapeutic agent­induced apoptosis of BaF3 cells.

Ecotropic viral integration site 1 regulates the progression of acute myeloid leukemia via MS4A3-mediated TGFß/EMT signaling pathway.

Acute myeloid leukemia (AML) is a type of malignant tumor that is caused by malignant clone hematopoietic stem cells. The ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which is highly expressed in AML, and its expression level has been associated with poor prognosis of AML. Previous studies have indicated that Evi1 may regulate cell proliferation, differentiation and apoptosis by inhibiting the membrane-spanning-4-domains subfamily-A member-3 (MS4A3) gene in AML. The aim of the present study was to investigate the role of Evi1 in the progression of AML. The results revealed that Evi1 was overexpressed in leukemia cells compared with normal T lymphocytes. MicroRNAs (miR)-133 and -431 that target Evi1 were investigated, and it was observed that there was a low expression of miR-431 in AML. The transfection of miR-431 was able to decrease the promoter methylation levels of the Evi1 gene in AML cells. The transfection of miR-431 also suppressed the migration and invasion of AML cells. The present study revealed that the transfection of miR-431 mimic was able to downregulate MS4A3 expression in AML cells. Furthermore, the expression levels of transforming growth factor ß (TGFß) and epithelial-to-mesenchymal transition (EMT) markers fibronectin, α-smooth muscle actin, and vimentin were downregulated following the transfection of miR-431 in AML cells. The overexpression of MS4A3 was also able to suppress miR-431-mediated inhibition of the expression of TGFß and EMT markers in AML cells. The addition of TGFß inhibited the downregulation of EMT markers by transfection of miR-431 in AML cells. The transfection of miR-431 suppressed the migration and invasion of AML cells, which was also abolished by the addition of TGFß. In conclusion, the results of the present study indicated that Evi1 may be a potential molecular target of leukemia therapy via MS4A3-mediated TGFß/EMT signaling pathway.