The regulation of stem cell fate is poorly understood. Genetic studies in lead to the hypothesis that a conserved cytoplasmic double-negative feedback loop consisting of the RNA-binding protein Trim71 and the let-7 microRNA controls the pluripotency and differentiation of stem cells. Although let-7-microRNA-mediated inhibition of Trim71 promotes differentiation, whether and how Trim71 regulates pluripotency and inhibits the let-7 microRNA are still unknown. Here, we show that Trim71 represses mRNA translation in mouse embryonic stem cells. Blocking this repression leads to a specific post-transcriptional increase of mature let-7 microRNAs, resulting in let-7-dependent stemness defects and accelerated differentiation in the stem cells. These results not only support the Trim71-let-7-microRNA bi-stable switch model in controlling stem cell fate, but also reveal that repressing the conserved pro-differentiation let-7 microRNAs at the mature microRNA level by Ago2 availability is critical to maintaining pluripotency.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906602 | PMC |
| http://dx.doi.org/10.7554/eLife.66288 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Temporal regulation of gene expression is required for developmental transitions, including differentiation, proliferation, and morphogenesis. In the nematode , heterochronic microRNAs (miRNAs) regulate the temporal expression of genes that promote animal development. The heterochronic miRNAs lin-4 and let-7 are required during different stages of larval development and are associated with the miRNA-specific Argonaute ALG-1.
View Article and Find Full Text PDFAn Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer Cells and .
Curr Protein Pept Sci
January 2025
Key Laboratory of Medical Cell Biology in Inner Mongolia, Clinical Medical Research Center, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia,010050, China.
Background: Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated.
View Article and Find Full Text PDFThe Effect of Atorvastatin on Oncogenic miRNAs in Hematological Malignancies: A Central Study.
Biomolecules
December 2024
Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
The efficacy of statins as anti-cancer drugs has been demonstrated in several malignancies but has been poorly investigated in hematological malignancies (HM). By studying its effect on oncogenic miRNAs, we investigated the effect of statin therapy on HM patients. The data were used to identify enriched pathways that were altered due to statin treatment.
View Article and Find Full Text PDFGastric cancer-derived exosomal let-7 g-5p mediated by SERPINE1 promotes macrophage M2 polarization and gastric cancer progression.
J Exp Clin Cancer Res
January 2025
Department of General Surgery, The Second Clinical Medical School, The Second Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu, 730000, China.
Background: Tumor-associated macrophages (TAMs), particularly M2-polarized TAMs, are significant contributors to tumor progression, immune evasion, and therapy resistance in gastric cancer (GC). Despite efforts to target TAM recruitment or depletion, clinical efficacy remains limited. Consequently, the identification of targets that specifically inhibit or reprogram M2-polarized TAMs presents a promising therapeutic strategy.
View Article and Find Full Text PDFIncreased expression of plasma mir-9-3p and let-7b-3p in methamphetamine use disorder and its clinical significance.
Sci Rep
December 2024
Department of Drug Prohibition and Public Security, Criminal Investigation Police University of China, Shenyang, 110035, China.
Methamphetamine use disorder has emerged as a significant public health concern globally. This study endeavors to elucidate the alterations in expression changes of miRNAs in the plasma of methamphetamine use disorder and elucidate the alterations in miRNA expression in the plasma of individuals with methamphetamine use disorder and investigate the relationship between these differentially expressed miRNAs and the disorder itself, cravings for methamphetamine, and associated mental disorders. Furthermore, the study seeks to clarify the expression of downstream target molecules of specific miRNAs in the plasma of methamphetamine use disorder, assess the diagnostic utility of these miRNAs and their target molecules, explore their potential as biomarkers, and identify potential targets for the diagnosis and treatment of methamphetamine use disorder.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!