Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of HNRNPA2B1-regulated miRNA targets in breast cancer cells

ABSTRACT: Higher N(6)-methyladenosine (m6A) was identified in selected primary microRNAs (pri-miRNAs) as associated with increased levels of the corresponding mature miRNA in MDA-MB-231 triple negative breast cancer (TNBC) cells (PMID: 25799998). HNRNPA2B1 is a reader of the m6A mark in pri-miRNAs and interacts directly with DGCR8 (a component of the nuclear DROSHA complex) to promote processing of pri-miRNAs to precursor-miRNAs (pre-miRNAs) (PMID: 26321680). We have preliminary data showing that HNRNPA2B1 is increased in TAM-resistant, ERα+ LCC9 cells derived from TAM-sensitive, ERα+ MCF-7 breast cancer cells. We found that high HNRNPA2B1 transcript levels in primary breast tumors are associated with reduced overall survival. We postulate that an increase in HNRNPA2B1 targets its binding to additional pri-miRNAs (not normally bound under wild type conditions), resulting in an increase in miRNAs, including those that promote TAM-resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122634 | GEO | 2019/07/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Sumoylated hnrnpa2b1 controls the sorting of miRNAs into two exosomes through binding to specific motifs

Project description:Exosomes are released by most cells to the extracellular environment, and are involved in cell-to-cell-communication. Exosomes contain specific repertoires of mRNAs, miRNAs and other non-coding RNAs that can be functionally transferred to recipient cells. However, the mechanisms that control the specific loading of RNA species into exosomes remain unknown. Here we describe short sequence motifs present in miRNAs that control their localization into exosomes. The protein hnRNPA2B1 specifically binds exosomal miRNAs through the recognition of these motifs and controls their loading into exosomes. Moreover, hnRNPA2B1 in exosomes is sumoylated, and sumoylation controls the binding of hnRNPA2B1 to miRNAs. The loading of miRNAs into exosomes can be modulated by mutagenesis of the identified motifs or changes in hnRNPA2B1 expression levels. These findings identify hnRNPA2B1 as a key player in miRNA sorting into exosomes and provide potential tools for the packaging of selected regulatory RNAs into exosomes and their use in biomedical applications.

2014-04-16 | PXD000350 | Pride

Nuclear HNRNPA2B1 HITS-CLIP and RNA-seq

Project description:To identify HNRNPA2B1 binding sites on endogenous nuclear RNAs, we performed HITS-CLIP for endogenous HNRNPA2B1 and RNA-seq to analyze the nuclear RNA under either METTL3 or HNRNPA2B1 depletion. Wild type MDA-MB-231 cells were subjected to the HITS-CLIP procedure on immunoprecipitated HNRNPA2B1 associated RNA obtained from the nuclear fraction (Licatalosi D, et al. 2008, Nature 456:464-U22). For RNA-seq, nuclear RNA was extracted from MDA-MB-231 or Hela cells knocked down for METTL3 or HNRNPA2B1.

2015-06-20 | E-GEOD-70061 | biostudies-arrayexpress

MeRIP-Seq map HNRNPA2B1 maintains MM tumorigenicity by m6A dependent stabilizing of mRNA

Project description:To investigated the mechanism of HNRNPA2B1 in MM tumorigenesis, performed m6A IP seq analysis (MeRIP-Seq) to identify the expression changes in stable HNRNPA2B1-knockdown MM cells.60 genes m6A with over 2-fold expression change in shHNRNPA2B compared with control in both ARP1 and H929 cells.44 differentially expressed genes (P<0.05) in both m6A and transcription in shHNRNPA2B compared with control in ARP1 cell.

2021-11-30 | GSE162745 | GEO

The Interplay between K63-linked Polyubiquitinated DDX17 and m6A-modified miRNAs Regulates Hypoxia-induced Tumor Initiation

Project description:DEAD-box RNA-binding proteins (RBPs) play a significant role in RNA metabolism to achieve cellular homeostasis, including miRNA biogenesis and transcription. Hypoxia induces stemness cell-like characteristics in cancer cells and promotes malignant progression. Despite the fact that hypoxia can induce the changes in protein and RNA modification, thereby regulating downstream gene expressions, how modifications at different molecular layers interplay with each other are poorly understood. Here we show that hypoxia induces HectH9-mediated K63-linked polyubiquitination of the DEAD-box protein DDX17 as well as reduces N6-methyladenosine (m6A) marks in pri-miRNAs. While m6A potentiates DDX17 binding to pri-miRNAs, decreased m6A modifications of pri-miRNAs and increased polyubiquitination of DDX17 under hypoxia lead to decreased DDX17 binding to pri-miRNAs binding. These events enhance the association of DDX17 with the ubiquitin receptor p300 and lead to a decrease in miRNA biogenesis, especially for miRNAs regulating stemness and stemness-related genes. In addition, polyubiquitinated DDX17 together with p300 upregulates H3K56Ac levels on the stemness and stemness-related genes, resulting in enhancement of tumor initiating ability. Post-transcriptionally, decreased miRNA production, including those targeting stemness genes or stemness-related genes, also facilitates tumor initiation. Together, hypoxia triggers DDX17 poly-ubiquitination, which orchestrates dual mechanisms to increase tumor initiating ability and promote tumor progression.

2018-03-09 | PXD006059 | JPOST Repository

DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression

Project description:Both N6-methyladenosine (m6A) mediates RNA fates and ubiquitin mediates protein fates play an important role in either physiology or pathology including cancer, yet how long noncoding RNAs (lncRNAs) are involved in a link of molecular fate between m6A and ubiquitin remains unknown. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer (DRAIC) to suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAIC physically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitin and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-type 1 insulin-like growth factor receptor (IGF1R) to lead to inhibition of ccRCC progression. Moreover, four m6A modification sites of IGF1R are identified and results in its mRNA degradation. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA expression in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1R axis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.

2024-04-26 | GSE262500 | GEO

DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression [m6A-seq]

2024-01-07 | GSE244892 | GEO

DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression [RNA-seq]

2024-01-07 | GSE244891 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and hnRNPA2B1-KO sw480 cell line Transcriptomes

Project description:HNRNPA2B1, an RNA-binding protein, plays a key role in primary microRNA processing, alternative splicing, mRNA metabolism and transport. Interestingly, hnRNPA2B1 also works as an N6-methyladenosine(m6A) reader and is critical during tumorigenesis of various tissue types. However, its role in colon cancer is still unclear. In this study, we aimed to elucidate the biological functions of hnRNPA2B1 and to explore its underlying mechanisms in colon cancer. Methods We examined the expression of hnRNPA2B1 in Oncomine and TCGA databases. Then verified the findings in colon cancer cells and clinical samples with western blotting and immunohistochemistry (IHC). We used CRISPR/Cas9 directed gene editing to knockout hnRNPA2B1 expression in human colon cancer cell line SW480 and carried out both in vivo and in vitro experiments. The results were further confirmed by RNA-seq analysis. We found that hnRNPA2B1 significantly promoted colon cancer cell proliferation both in vitro and in vivo, while knockout of hnRNPA2B1 induced apoptosis and cell cycle arrest in SW480. RNA-seq analysis revealed that the ERK/MAPK pathway was activated by hnRNPA2B1 upregulation. In addition, both hnRNPA2B1 and MAPK pathway were activated in clinical colon cancer specimens and positively correlated. Mechanistically, hnRNPA2B1 appeared to be an upstream regulator of the ERK/MAPK pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1. Taken together, our data demonstrated that the RNA-binding protein hnRNPA2B1 promotes cell proliferation and regulates cell cycle and apoptosis of human colon cancer by activating the ERK/MAPK signaling, which may provide a new insight into the development of hnRNPA2B1 as a potential therapeutic target for treatment of colon cancer.

2021-06-09 | GSE169211 | GEO

Nuclear HNRNPA2B1 HITS-CLIP and RNA-seq

2015-06-20 | GSE70061 | GEO

Comparative gene expression profiling analysis of RNA-seq data for U251 control and hnRNPA2B1 knockdown cells

Project description:Gliomas are the most common type of primary brain tumors, accounting for approximately 80% of all malignant brain tumors. The m6A RNA methylation process, mediated by various m6A regulatory genes, has been implicated in promoting the development and progression of tumors. However, the understanding of its involvement in glioma remains limited. Therefore, RNA sequencing (RNA-seq) was performed in U251 cells following hnRNPA2B1 knockdown, as it functions as an oncogene and is one of the m6A reader proteins.

2024-05-01 | GSE240809 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data