Degradation of AGO2 by TRIM25 drives cancer progression and chemotherapy resistance
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE290308 | GEO | 2026/04/25
REPOSITORIES: GEO
Similar Datasets
Project description:To gain deeper insights into the role of Trim25 expression in T cells in regulating tumor microenvironment dynamics, we performed single-cell RNA sequencing on purified CD45+ immune cells isolated from MC38 xenografts harvested from either Trim25 cKO or WT C57BL/6 mice.
2025-09-15 | GSE281314 | GEO
Project description:Activating mutation of KIT is well known as a key molecular event for the development of gastrointestinal stromal tumors(GISTs). Dysregulation of microRNAs(miRNA) might elucidate KIT mutation, KIT overexpression and the resulting tumorigenesis in GIST. Herein we identified miRNA expression profiles that associated with KIT mutation and KIT overexpression in GIST by miRNA microarrays and Real-time PCR in GISTs. The potentially target genes of selected miRNAs were analyzed by bioinformatic techniques with GO and KEGG pathway analysis. We showed that 6 miRNAs were differentially expressed in CD117IHC+/KITmutant GISTs compared to CD117IHC-/wild-type GISTs. Of these, 2 miRNAs including miR-483-3p and miR-589 were up-regulated, while the other 4 miRNAs including miR-140-5p, miR-148b-3p, miR-1587 and miR-4507 were down-regulated. GO and KEGG analysis demonstrated that miRNAs with significant change were involved in regulation of target genes related to the development of GIST. Among the candidate miRNAs studied, miR-148b-3p and miR-140-5p may be involved in GIST tumorigenesis via targeting mutant KIT or via intermediate molecules of PDGFRA, PI3K-AKT and MAPK pathway, such as AKT2, MAPK1, MAPK10, STAT5A, SMAD4, SMAD5 and PTEN. Furthermore, the reduced expression of miR-140-5p and miR-148b-3p were inversely correlated with high-risk grade, recurrence and metastasis of GIST. The current findings indicated that miR-148b-3p and miR-140-5p were not only involved in tumorigenesis of GIST, but might also participate in the progression of GIST and could be considered as novel biomarkers for potentially predicting the prognosis of GIST.
2018-04-25 | GSE73346 | GEO
Project description:Meis1 is a transcription factor involved in a broad range of functions including development and proliferation and has been previously shown to harness cell cycle progression. This study aimed to investigate the regulation of Meis1 by long non-coding RNAs (lncRNAs) and their sponged microRNAs (miRNAs) and hence the impact of this regulatory axis on cell proliferation. Using in-silico analysis, miR-499-5p was predicted to target Meis1 and Malat1 was predicted and previously proven to sponge miR-499-5p. We showed that forcing the expression of miR-499-5p downregulates Meis1 expression in C166 cell line by directly binding to its 3’UTR. In addition, Malat1 knockdown significantly increases miR-499-5p expression, subsequently suppressing Meis1 mRNA and protein expression levels. Furthermore, the impact of manipulating the Malat1/miR-499-5p/Meis1 axis on cellular proliferation was assessed using the BrdU incorporation assay. We demonstrated that upon knockdown of Malat1, mimicking with miR-499-5p, or knockdown of Meis1, cell proliferation was induced. Gene Ontology, KEGG and Reactome enrichment analyses were performed on proteins detected by mass spectrometry following manipulation of the Malat1/miR-499-5p/Meis1 axis. The data revealed a multitude of differentially expressed proteins (DEPs) significantly enriched in processes related to cell cycle, cell division and proliferation. These DEPs were also involved in key signaling pathways, such as Wnt and mTOR, known to play critical roles in cell proliferation and cell cycle. Finally, since Malat1 and miR-499-5p are conserved in humans and mice, we examined the expression pattern of both non-coding RNAs (ncRNAs) in the hearts of neonatal, postnatal, and adult mice, representing models of proliferative and non-proliferative tissues. We demonstrated a paradoxical expression pattern, where Malat1 is underexpressed while miR-499-5p is overexpressed in proliferative neonatal cardiomyocytes. Collectively, our findings confirm that Malat1 sponges miR-499-5p which directly regulates Meis1, and that Malat1/miR-499-5p/Meis1 axis has a pivotal influence on cellular proliferation.
2025-05-07 | PXD054558 | Pride
Project description:Background/Objective: Quantitative real-time PCR (RT-qPCR) is widely used in miRNA expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. A literature search in PubMed revealed that no study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference genes for miRNA expression studies by RT-qPCR in urothelial carcinoma. Methods: Candidate reference miRNAs were selected from 24 papillary urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. Principal Findings: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-3p, miR-151-5p, miR-181a, miR-181b miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. Conclusions: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-125a-5p, miR-148b, miR-151-3p, and miR-151-5p) or three (miR-148b, miR-874, miR-181b) miRNA reference genes is recommended for normalization. Candidate reference miRNAs (for RT-qPCR analysis) were selected from 24 papillary urothelial carcinoma and normal bladder tissue samples by miRNA microarrays.
2013-02-26 | E-GEOD-36121 | biostudies-arrayexpress
Project description:Exogenous mRNAs require cellular machinery for delivery and translation but also encounter inhibitory factors. To investigate their regulation, we performed genome-wide CRISPR screens with in vitro-transcribed mRNAs in lipid nanoparticles (LNPs). Heparan sulfate proteoglycans and vacuolar ATPase were identified as mediators of LNP uptake and endosomal escape, respectively. TRIM25 emerged as a key suppressor inducing turnover of both linear and circular mRNAs. Endoribonucleases, N4BP1 and KHNYN, along with ZAP, act redundantly in TRIM25-dependent surveillance. TRIM25 specifically targets mRNAs delivered via endosomes, and its RNA affinity increases at acidic pH, suggesting activation by protons released from ruptured endosomes. N1-methylpseudouridine (m1Ψ) modification reduces TRIM25’s RNA binding, helping RNAs evade its suppressive effect. This study comprehensively maps cellular pathways regulating LNP-mRNAs, offering insights into RNA immunity and therapeutics.
2025-04-04 | GSE264535 | GEO
Project description:Degradation of AGO2 by TRIM25 drives cancer progression and chemotherapy resistance
| PRJNA1227454 | ENA
Project description:TRIM25 E3 ubiquitin ligase is a new RNA-binding protein. We present the first high-throughput analysis of the molecular interactomes of TRIM25. We show that TRIM25 is a bona fide RNA-binding protein that interacts with numerous coding and non-coding transcripts. This suggests that TRIM25 could play a role in the regulation of RNA metabolism.
2018-07-27 | GSE104949 | GEO
Project description:Background/Objective: Quantitative real-time PCR (RT-qPCR) is widely used in miRNA expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. A literature search in PubMed revealed that no study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference genes for miRNA expression studies by RT-qPCR in urothelial carcinoma. Methods: Candidate reference miRNAs were selected from 24 papillary urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. Principal Findings: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-3p, miR-151-5p, miR-181a, miR-181b miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. Conclusions: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-125a-5p, miR-148b, miR-151-3p, and miR-151-5p) or three (miR-148b, miR-874, miR-181b) miRNA reference genes is recommended for normalization.
2013-02-26 | GSE36121 | GEO
Project description:TRIM25 is an RNA-binding ubiquitin E3 ligase with central but poorly understood roles in the innate immune response to RNA viruses. The link between TRIM25’s RNA binding and its role in innate immunity has not been established. Thus, we utilized a multitude of biophysical techniques to identify key RNA-binding residues of TRIM25 and developed an RNA-binding deficient mutant (TRIM25-m9). Using iCLIP2 in virus-infected and uninfected cells, we identified TRIM25’s RNA sequence and structure specificity, that it binds specifically to viral RNA, and that the interaction with RNA is critical for its antiviral activity.
2024-09-20 | GSE276465 | GEO