MicroRNAs: pivotal regulators in acute myeloid leukemia.

MicroRNAs are a class of small non-coding RNAs that are 19-22 nucleotides in length and regulate a variety of biological processes at the post-transcriptional level. MicroRNA dysregulation disrupts normal biological processes, resulting in tumorigenesis. Acute myeloid leukemia is an invasive hematological malignancy characterized by the abnormal proliferation and differentiation of immature myeloid cells. Due to the low 5-year survival rate, there is an urgent need to discover novel diagnostic markers and therapeutic targets. In recent years, microRNAs have been shown to play important roles in hematological malignancies by acting as tumor suppressors and oncogenes. MicroRNAs have the potential to be a breakthrough in the diagnosis and treatment of acute myeloid leukemia. In this review, we summarize the biology of microRNAs and discuss the relationships between microRNA dysregulation and acute myeloid leukemia in the following aspects: signaling pathways, the abnormal biological behavior of acute myeloid leukemia cells, the clinical application of microRNAs and competing endogenous RNA regulatory networks.

The Expression and Clinical Significance of MicroRNA-409-3p in Acute Myeloid Leukemia.

BACKGROUND: MicroRNA-409-3p, is down-regulated in a variety of malignant diseases. However, the expression level and clinical value of microRNA-409-3p in acute myeloid leukemia has not yet been systematically studied. METHODS: We collected 88 bone marrow samples derived from 73 patients with acute myeloid leukemia and 15 healthy controls. Then we evaluated the expression of microRNA-409-3p by quantitative real-time PCR. RESULTS: The results revealed that compared with the healthy controls, microRNA-409-3p expression in a newly diagnosed group was significantly lower (p < 0.001). In addition, the microRNA-409-3p expression in the complete remission group was strikingly higher compared to that of the newly diagnosed group (p < 0.001). There was a correlation between microRNA-409-3p expression and white blood cells (p = 0.021). Most importantly, the micro-RNA-409-3p low expression group indicated a shorter event-free survival compared with microRNA-409-3p high expression group by using Kaplan-Meier analysis (p < 0.0438). CONCLUSIONS: The microRNA-409-3p expression level could be a novel potential biomarker for acute myeloid leukemia diagnosis and prognosis, providing a new therapeutic strategy for acute myeloid leukemia treatment.

Emerging function and potential diagnostic value of circular RNAs in cancer.

As a novel class of endogenous RNAs, circRNAs, have a covalently closed continuous loop, with neither a 5'to 3'polarity, nor a polyadenylated tail. Numerous circRNAs have been characterized by abundance, stabilization, conservation, and exhibit tissue/developmental stage-specific expression. Furthermore, circRNAs play vital roles in tumorigenesis and metastasis, such as functioning as a ceRNA or miRNA sponge, interacting with protein and encoding protein. Increasing evidence has revealed that it potentially serves as a required novel biomarker for cancer diagnosis. This review summarized the latest research on circRNAs, including its classification and biogenesis, mechanism and functions, as well as circRNAs in different cancers, as a potential biomarker.

Association between alkaline phosphatase to albumin ratio and mortality among patients with sepsis.

The alkaline phosphatase-to-albumin ratio (APAR) is correlated to worse prognosis in coronary artery disease, cancer, and acute renal failure. However, the relationship between APAR and sepsis prognosis has received little research. The content of this research was to investigate the prognostic relationship between APAR and sepsis. And validate the stability of the correlation in 90-days and 1-year mortality. Retrospective cohort research was conducted basing MIMIC-IV database (version 2.0). The hazard ratio (HR) and 95% confidence interval (Cl) were computed using multivariate Cox regression analysis. In addition, plots of survival curves and subgroup analyzes were conducted. Receiver operating characteristic (ROC) curves were also used. 9741 participants were included in this investigation. The 90-days mortality was 32.8%, and the 1-year mortality was 42.0%. After controlling for confounders, the adjusted HRs (95% CI) for tertile 2 (2.2-3.8) and tertile 3 (> 3.8) were 1.37 (1.25-1.51) and 1.74 (1.58-1.91), respectively. The Kaplan-Meier curve analysis showed a higher probability of 90-days death in the higher APAR group. The area under the curve (AUC) of APAR was 0.674 and could reach 0.709 after combining the Oxford Acute Severity of Illness Score (OASIS). This study demonstrates that APAR is significantly related to bad clinical outcomes in sepsis.

Molecular mechanisms and clinical applications of exosomes in prostate cancer.

Prostate cancer (PC) is a common tumor in men, and the incidence rate is high worldwide. Exosomes are nanosized vesicles released by all types of cells into multiple biological fluid types. These vesicles contribute to intercellular communication by delivering both nucleic acids and proteins to recipient cells. In recent years, many studies have explored the mechanisms by which exosomes mediate the epithelial-mesenchymal transition, angiogenesis, tumor microenvironment establishment, and drug resistance acquisition in PC, and the mechanisms that have been identified and the molecules involved have provided new perspectives for the possible discovery of novel diagnostic markers in PC. Furthermore, the excellent biophysical properties of exosomes, such as their high stability, high biocompatibility and ability to cross biological barriers, have made exosomes promising candidates for use in novel targeted drug delivery system development. In this review, we summarize the roles of exosomes in the growth and signal transmission in PC and show the promising future of exosome contributions to PC diagnostics and treatment.

A circular RNA from NFIX facilitates oxidative stress-induced H9c2 cells apoptosis.

Myocardial infarction is the leading cause of death worldwide, and cardiomyocyte apoptosis during myocardial infarction and reperfusion is a significant factor of poor prognosis. As important regulatory molecules, biofunctions of circRNAs in the pathogenesis of myocardial infarction remain elusive. To confirm the expression level and biological function of circNFIX in cardiomyocytes upon oxidative stress. Divergent polymerase chain reaction and Sanger sequencing were performed to verify the circular structure. The stability of circNFIX was confirmed by RNase R treatment and actinomycin D assay. In order to simulate oxidative stress during myocardial infarction, H9c2 cells were subjected to hydrogen peroxide and hypoxia stimulation. In vivo, mouse models of myocardial ischemia were established. The biological function of circNFIX in cardiomyocytes was investigated through loss- and gain-of-function assays, and cardiomyocyte apoptosis level was detected by the terminal deoxyribonucleotidyl transferase-mediated TdT-mediated dUTP nick end labeling assay and Western blot. CircNFIX is abundant, conserved, and stable in H9c2 cells. The expression of circNFIX was significantly downregulated in cardiomyocytes subjected to oxidative stress. Enforced CircNFIX promotes H9c2 cells apoptosis induced by hydrogen peroxide, in sharp contrast to circNFIX knockdown. In this study, we found that circNFIX served as a pro-apoptosis factor in cardiomyocyte apoptosis. CircNFIX possesses potential to be the biomarker and therapeutic target in myocardial infarction.