miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

Identification of the Shared Gene Signatures of HCK, NOG, RNF125 and Biological Mechanism in Pediatric Acute Lymphoblastic Leukaemia and Pediatric Sepsis.

The shared mechanisms between pediatric acute lymphoblastic leukaemia (ALL) and pediatric sepsis are currently unclear. This study was aimed to explore the shared key genes of pediatric ALL and pediatric sepsis. The datasets involved were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control samples in GSE13904 and GSE79533 were intersected. The least absolute shrinkage and selection operator (LASSO) and the boruta analyses were performed in GSE13904 and GSE79533 separately based on shared DEGs, and shared key genes were obtained by taking the intersection of sepsis-related key genes and ALL-related key genes. Three shared key genes (HCK, NOG, RNF125) were obtained, that have a good diagnostic value for both sepsis and ALL. The correlation between shared key genes and differentially expressed immune cells was higher in GSE13904 and conversely, the correlation of which was lower in GSE79533. Suggesting that the sharing key genes had a different impact on the immune environment in pediatric ALL and pediatric sepsis. We make the case that this study provides a new perspective to study the relationship between pediatric ALL and pediatric sepsis.