Expression data from lung cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165453 | GEO | 2022/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:ALKBH5 (AlkB homolog 5) has been identified as a eukaryotic demethylase, which catalyzes N6 adenosine. N6-methyladenosine (m6A) is oxidatively demethylated by ALKBH5 with α-ketoglutarate as a substrate and Fe (II) as a coenzyme. We used microarrays to detail the differential gene expression by ALKBH5 knockdown in lung cancer cell lines.
2022-06-01 | GSE165454 | GEO
Project description:Knocking down ALKBH5 in Glioma Stem Cells resulted in an altered gene expression profile N6-methyl-adenosine (m6A) is the most prevalent internal chemical modification of mRNAs in eukaryotes. In mammals, m6A installed by m6A methyltransferases METTL3 and METTL14 is erased by two members of the AlkB family of nonheme Fe(II)/a-ketoglutarate (a-KG)-dependent dioxygenases, fat-mass and obesity associated protein (FTO) or ALKBH5. ALKBH5 affects nuclear RNA export and metabolism, gene expression and mouse fertility. To date, little is known about the biological significance of m6A in human cancer. We found that ALKBH5 is highly expressed in human glioblastoma stem cells which are resistant to conventional therapy and give rise to glioblastoma recurrence by sustaining long-term tumor growth. Global manipulation of the m6A modification by depleting ALKBH5 resulted in altered gene expression including subsets of genes enriched in "Cell Cycle", "DNA Replication, Recombination, and Repair" and "Cellular Assembly and Organization". Knockdown of ALKBH5 expression in human glioblastoma stem cells significantly reduced their self-renewal ability as a result of inhibition of cell cycle progression. This study demonstrated the important role of m6A modification in human glioblastoma development.
2017-03-28 | GSE93054 | GEO
Project description:N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as a new mammalian demethylase that oxidatively removes the m6A modification in mRNA in vitro and inside cells. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1552 differentially expressed genes which cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. We show that Alkbh5-deficiency impacts the expression levels of some of these mRNAs, supporting the observed phenotype. The discovery of this new RNA demethylase strongly suggests that the reversible m6A modification plays fundamental and broad functions in mammalian cells. RNA-seq in two cell types
2013-02-15 | E-GEOD-40132 | biostudies-arrayexpress
Project description:N6-methyladenosine (m6A) modification is implicated in the tumorigenicity of hepatocellular carcinoma (HCC). AlkB homolog 5 (ALKBH5) is one of the m6A demethylases, and it has not been well characterized in HCC. In our study we clarify the biological roles and potential mechanisms of ALKBH5 in HCC. We identify the expression profile of ALKBH5 in HCC and find that it serves as an independent prognostic factor of HCC survival. It impacts the proliferation and invasion capability of HCC cells in vitro and in vivo. ALKBH5-mediated m6A demethylation leads to a post-transcriptional modulation of LYPD1. In addition, we reveal the tumor-related behaviors of LYPD1.
2020-08-11 | GSE149510 | GEO
Project description:In addition to the role of antioxidant, ascorbic acid (reducing Vitamin C) is an important cofactor for Fe2+ and α-ketoglutarate (α-KG) dependent dioxygenases (Fe2+/α-KGDDs) that comprise many diverse enzymes, including collagen prolyl hydroxylases, jmjC (Jumonji C) domain containing histone demethylases, Ten-eleven translocation (TET) 5-methyl cytosine (5mC) dioxygenases, and N6-methyl adenosine (m6A) demethylase FTO and ALKBH5. Ascorbic acid was reported to induce global epigenetic reprogramming. Here we optimized the library construction flow chart of single-stranded DNA profiling method KAS-seq and utilized KAS-seq to profile transient chromatin states changes upon ascorbic acid treatment for 10 min. We identified several critical pathways affected by ascorbic acid treatment, providing some clues for explaining the reported positive impact of anti-cancer, anti-depression, and anti-obesity for taking ascorbic acid.
2023-07-25 | GSE237843 | GEO
Project description:N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as a new mammalian demethylase that oxidatively removes the m6A modification in mRNA in vitro and inside cells. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1552 differentially expressed genes which cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. We show that Alkbh5-deficiency impacts the expression levels of some of these mRNAs, supporting the observed phenotype. The discovery of this new RNA demethylase strongly suggests that the reversible m6A modification plays fundamental and broad functions in mammalian cells.
2013-02-15 | GSE40132 | GEO
Project description:To identify potential target mRNAs that are demethylated by ALKBH5, meRIP-seq with a m6A antibody was conducted in 143B osteosarcoma cells transfected with scrambled or ALKBH5-siRNA.
2022-06-28 | GSE154529 | GEO
Project description:Objectives: To investigate the role of ALKBH5 in fibroblasts during post-myocardial infarction (MI) repair. Background: N6-methyladenosine (m6A) mRNA modification has been shown to play an important role in cardiovascular diseases. The RNA demethylase, AlkB homolog 5 (ALKBH5), is an m6A "eraser" that is responsible for decreased m6A methylation. However, its role in cardiac fibroblasts during the post-MI healing process remains elusive. Methods: MI was mimicked by permanent left anterior descending artery ligation in global ALKBH5-knockout, ALKBH5-knockin, and fibroblast-specific ALKBH5-knockout mice to study the function of ALKBH5 during post-MI collagen repair. Methylated RNA immunoprecipitation sequencing was performed to explore potential ALKBH5 targets. Results: Dramatic alterations in ALKBH5 expression were observed during the early stage post-MI and in hypoxic fibroblasts. Global ALKBH5 knockin reduced infarct size and improved cardiac function after MI. The global and fibroblast-specific ALKBH5-knockout mice both exhibited low survival rates along with poor collagen repair, impaired cardiac function, and cardiac rupture. Both in vivo and in vitro ALKBH5 loss led to impaired fibroblast activation and decreased collagen deposition. Additionally, hypoxia, but not TGF-β1 or Ang II, upregulated ALKBH5 expression in myofibroblasts in a HIF-1α-dependent transcriptional manner. Mechanistically, ALKBH5 promoted the stability of ErbB4 mRNA and the degradation of ST14 mRNA via m6A demethylation. Fibroblast-specific ErbB4 overexpression ameliorated the impaired fibroblast-to-myofibroblast transformation and poor post-MI repair due to ALKBH5 knockout. Conclusions: Fibroblast ALKBH5 positively regulates post-MI healing via post-transcriptional modification and stabilization of ErbB4 mRNA in an m6A-dependent manner. Targeting ALKBH5/ERBB4 may be a potential therapeutic option for post-MI cardiac rupture.
2023-10-01 | GSE226415 | GEO
Project description:Reflux of bile acids and subsequent caudal-related homeobox 2 (CDX2) activation contribute to gastric intestinal metaplasia (IM), which is a precursor of gastric cancer. However, the underlying mechanism by which bile acids cause this is not entirely clear. Here we demonstrated that alkylation repair homolog protein 5 (ALKBH5), which is a major RNA N6-adenosine demethylase, was required for bile acid-induced gastric IM. Mechanistically, we revealed the N6-methyladenosine (m6A) modification profile in gastric IM for the first time and identified ZNF333 as a bona fide m6A target of ALKBH5. ALKBH5 was shown to demethylate ZNF333 mRNA, leading to enhanced ZNF333 expression by abolishing m6A-YTHDF2-dependent mRNA degradation. In addition, ALKBH5 activated CDX2 and downstream intestinal markers by targeting the ZNF333/CYLD axis and activating NF-κB signaling. Reciprocally, p65, which is the key transcription factor of the canonical NF-κB pathway, enhanced the transcription activity of ALKBH5 in the nucleus, thus forming a positive feed-forward circuit. In addition, ALKBH5 levels were positively correlated with ZNF333 and CDX2 in IM tissues, indicating a significant clinical relevance. Collectively, our findings suggest an m6A modification-associated positive feed-forward loop between ALKBH5 and NF-κB signaling is involved in the generation of the IM phenotype from gastric epithelial cells. Targeting the ALKBH5/ZNF333/CYLD/CDX2 axis might be a useful therapeutic strategy for gastric IM in patients with bile regurgitation.
2021-10-14 | GSE179185 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal modification in the messenger RNA (mRNA) of all higher eukaryotes. This modification has been shown to be reversible in mammals; it is installed by a methyltransferase heterodimer complex of METTL3 and METTL14 bound with WTAP, and reversed by iron(II)- and α-ketoglutarate-dependent demethylases FTO and ALKBH5. This modification exhibits significant functional roles in various biological processes. The m6A modification as a RNA mark is recognized by reader proteins, such as YTH domain family proteins and HNRNPA2B1; m6A can also act as a structure switch to affect RNA-protein interactions for biological regulation. In Arabidopsis thaliana, the methyltransferase subunit MTA (the plant orthologue of human METTL3, encoded by At4g10760) was well characterized and FIP37 (the plant orthologue of human WTAP) was first identified as the interacting partner of MTA. Here we report the discovery and characterization of reversible m6A methylation mediated by AtALKBH10B (encoded by At4g02940) in A. thaliana, and noticeable roles of this RNA demethylase in affecting plant development and floral transition. Our findings reveal potential broad functions of reversible mRNA methylation in plants. m6A peaks were identified from wild type Columbia-0 and atalkbh10b-1 mutant in two biological replicates
2016-03-24 | E-GEOD-79523 | biostudies-arrayexpress