Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The miR-194-5p/BCLAF1 module is responsible for maturation block, cell fate and treatment susceptibility in AML.

ABSTRACT: miRNAs deregulation contributes to cancer. miR-194-5p is up-regulated by the HDAC inhibitor (HDACi) SAHA, negatively modulating BCL2-associated transcription factor 1 (BCLAF1). We prove that the miR-194-5p/BCLAF1 equilibrium regulates differentiation, survival and self-renewal of normal progenitors and acute myeloid leukemia (AML) blasts. This equilibrium is perturbed in AMLs resulting in highly expressed BCLAF1, suppression of miR194-5p, consequently, locking cells into an immature, potentially ‘immortal’ state. HDACis reverse this scenario relocating BCLAF1 from the nucleus to a peri-membrane ring-like cytoplasmic structure, sensitizing the cells to differentiation or apoptosis. miR-194-5p and BCLAF1 are significantly deregulated in a cohort of 60 primary AMLs and get restored by HDACi. Our findings connect responsiveness to treatment to re-instatement of miR-194-5p/BCLAF1 balance. These findings might be exploited for (epi-based) anti-leukemia therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76426 | GEO | 2017/12/20

SECONDARY ACCESSION(S): PRJNA307259

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

U937 miR-194-5p (UmiR-194-5p) vs U937 miR-194-5p (UmiR-194-5p) treated with MS275 (SNDX 275;Entinostat)

Project description:Transcriptional profiling of U937 miR-194-5p (UmiR-194-5p) vs U937 miR-194-5p (UmiR-194-5p) treated with MS275 (SNDX 275;Entinostat) for 24 h at 5uM concetration

2017-05-22 | GSE73647 | GEO

U937 miR-194-5p (UmiR-194-5p) vs U937 miR-194-5p (UmiR-194-5p) treated with SAHA (Vorinostat; suberoylanilide hydroxamic acid)

Project description:Transcriptional profiling of U937 miR-194-5p (UmiR-194-5p) vs U937 miR-194-5p (UmiR-194-5p) treated with SAHA (Vorinostat; suberoylanilide hydroxamic acid) for 24 h at 5uM concetration

2017-05-22 | GSE73648 | GEO

Homo sapiens

Project description:U937 miR-194-5p (UmiR-194-5p) vs U937 miR-194-5p (UmiR-194-5p) treated with MS275 (SNDX 275 Entinostat)

| PRJNA297483 | ENA

U937 scramble (Usc) vs U937 miR-194-5p (UmiR-194-5p)

Project description:Transcriptional profiling of U937 scramble vs U937 miR-194-5p (UmiR-194-5p)

2017-05-22 | GSE73646 | GEO

Homo sapiens

Project description:U937 miR-194-5p (UmiR-194-5p) vs U937 miR-194-5p (UmiR-194-5p) treated with SAHA (Vorinostat suberoylanilide hydroxamic acid)

| PRJNA297482 | ENA

Lysine tRNA fragments and miR-194-5p co-regulate hepatic steatosis via β-Klotho and Perilipin 2 (RNA)

Project description:Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5’tRF transfer RNA fragments and microRNA miR-194-5p. Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5’tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5’tRF levels while increasing lipid accumulation. Importantly, transfecting fattened cells with a synthetic LysTTT-5’tRF mimic elevated mRNA levels of the metabolic regulator β-Klotho while decreasing triglyceride amounts by 30% within 24 hours. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5’tRF levels. The different yet complementary roles of miR-194-5p and LysTTT-5’tRF offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis.

2024-01-31 | GSE248320 | GEO

Lysine tRNA fragments and miR-194-5p co-regulate hepatic steatosis via β-Klotho and Perilipin 2 (small RNA II)

2024-01-31 | GSE248319 | GEO

Lysine tRNA fragments and miR-194-5p co-regulate hepatic steatosis via β-Klotho and Perilipin 2 (small RNA I)

2024-01-31 | GSE248317 | GEO

Expression data after BCLAF1-L knockdown in human RKO cells

Project description:Bcl-2-accociated transcription factor 1(BCLAF1) has been reported to be involved in diverse biological processes. Alternative splicing leads to mutiple transcript virants in human cells and we are interested in functions of its full length isoform(BCLAF1-L) in human colon cancer cells, thus to understanding its role in colon cancer progression. We used microarray to detail the global programme of gene expression after BCLAF1-L knockdown(sh-BCLAF1-L#1) in RKO cells and identified distinct classes of up-regulated or down-regulated genes impaired by its inhibition, when comparing with the control group(sh-Luci). RKO cells were infected with retroviruses either expressing control (sh-Luci) or BCLAF1-L knockdown (sh-BCLAF1-L#1). Medium was replaced 24h after infection, and infected cells were selected by the addition of puromycin (2ug/ml) for 72-96h. Then cells were havested for RNA extraction and hybridization on Affymetrix microarrays.

2013-12-05 | E-GEOD-52990 | biostudies-arrayexpress

Homo sapiens

Project description:U937 scramble (Usc) vs U937 miR-194-5p (UmiR-194-5p)

| PRJNA297481 | ENA