Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.
Although the incidence of pancreatitis was higher, the overall stone clearance rate and risk of bleeding was lower with EPBD compared to EST.
Long noncoding RNAs (lncRNAs) are emerging as important regulators in mammalian development, but little is known about their roles in monocyte/macrophage differentiation. Here we identified a long noncoding monocytic RNA (lnc-MC) that exhibits increased expression during monocyte/macrophage differentiation of THP-1 and HL-60 cells as well as CD34؉ hematopoietic stem/progenitor cells (HSPCs) and is transcriptionally activated by PU.1. Gain-and loss-of-function assays demonstrate that lnc-MC promotes monocyte/macrophage differentiation of THP-1 cells and CD34 ؉ HSPCs. Mechanistic investigation reveals that lnc-MC acts as a competing endogenous RNA to sequester microRNA 199a-5p (miR-199a-5p) and alleviate repression on the expression of activin A receptor type 1B (ACVR1B), an important regulator of monocyte/macrophage differentiation. We also noted a repressive effect of miR-199a-5p on lnc-MC expression and function, but PU.1-dominant downregulation of miR-199a-5p weakens the role of miR-199a-5p in the reciprocal regulation between miR-199a-5p and lnc-MC. Altogether, our work demonstrates that two PU.1-regulated noncoding RNAs, lnc-MC and miR-199a-5p, have opposing roles in monocyte/macrophage differentiation and that lnc-MC facilitates the differentiation process, enhancing the effect of PU.1, by soaking up miR-199a-5p and releasing ACVR1B expression. Thus, we reveal a novel regulatory mechanism, comprising PU.1, lnc-MC, miR-199a-5p, and ACVR1B, in monocyte/macrophage differentiation.H ematopoiesis is a highly orchestrated process wherein the pluripotent self-renewing hematopoietic stem cells (HSCs) give rise to all blood cell lineages, including monocytes/macrophages (1). Monocytes/macrophages are mononuclear phagocytes that play crucial roles in innate immunity and the inflammatory response, and defects in their biogenesis and function can contribute to a broad spectrum of pathologies (2, 3). Control of monocyte/macrophage differentiation is a complex process requiring the coordinated expression of stage-specific transcription factors, cytokines, and noncoding RNAs (4, 5).PU.1 is a hematopoiesis-specific transcription factor that binds to a purine-rich sequence (GAGGAA) and regulates lineage-specific gene expression (6). Homozygous PU.1-deficient mice died at a late gestational stage, and PU.1 mutant embryos exhibited a defect in the generation of progenitors for monocytes and granulocytes (7). High expression of PU.1 in granulocyte-macrophage progenitors (GMPs) antagonizes C/EBP␣ function and favors monocyte development. Conversely, GMPs with low expression of PU.1 commit to granulocyte differentiation (8). In addition, transcription factors RUNX1, KLF4, and MafB are important regulators in monocyte/macrophage development (9-11). Colonystimulating factors (CSF), including granulocyte-macrophage CSF, granulocyte CSF, and CSF-1, also play fundamental roles in the early and late stages of the monocyte/macrophage differentiation process (12).MicroRNAs (miRNAs) are short (20-to 24-nucleotide [nt]) noncoding RNAs tha...
Strand-selection is the final step of microRNA biogenesis in which functional mature miRNAs are generated from one or both arms of precursor. The preference of strand-selection is diverse during development and tissue formation, however, its pathological effect is still unknown. Here we find that two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, are inversely expressed and play exactly opposite roles in gastric cancer progression. Higher-5p with lower-3p expression pattern is significantly correlated with higher TNM stages and poor prognosis of gastric cancer patients. The increase of miR-574-5p/-3p ratio, named miR-574 arm-imbalance is partially due to the dynamic expression of their highly complementary targets in gastric carcinogenesis, moreover, the arm-imbalance of miR-574 is in turn involved and further promotes gastric cancer progression. Our results indicate that miR-574 arm-imbalance contribute to gastric cancer progression and re-modification of the miR-574-targets homeostasis may represent a promising strategy for gastric cancer therapy.
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