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NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1) [lncRNA-seq]

ABSTRACT: NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1) [lncRNA-seq]

PROVIDER: PRJNA1202133 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31811209_1.fastq.gz	Fastqsanger.gz
	SRR31811209_2.fastq.gz	Fastqsanger.gz
	SRR31811210_1.fastq.gz	Fastqsanger.gz
	SRR31811210_2.fastq.gz	Fastqsanger.gz

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NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1) [lncRNA-seq]

Project description:Natural killer cells (NK cells) play a critical role in the surveillance of tumor immunity. However, NK cell-based immunotherapy, including autologous and allogeneic NK cell reinfusion, has not brought significant clinical benefits to patients. To identify factors that control the intrinsic cytotoxicity of NK cells, we utilized the histone deacetylase inhibitor valproic acid (VPA) to develop a NK cell cytotoxicity suppression model. With RNA-seq and functional assays, we identified a previously uncharacterized lncRNA, NKCLR3 (NK cytotoxicity-associated long noncoding RNA 3), as a negative regulatory factor of NK cell-mediated cytotoxicity. NKCLR3 was significantly upregulated in VPA-treated NK cells and was negatively associated with the cytotoxicity of NK cells. Knockdown of NKCLR3 enhanced antitumor activity in NK-92MI cells. Using reverse transcription-associated capture sequencing (RAT-seq), we found that NKCLR3 functioned by targeting the Natural cytotoxicity triggering receptor 1 (NCR1) gene, which encodes the activating receptor NKp46 involved in the natural cytotoxicity. Mechanistic studies revealed that NKCLR3 interacted with the regulatory elements of NCR1 and blocked the formation of an intrachromosomal interaction that is required for optimal expression of NCR1. In addition, NKCLR3 inhibited the synthesis of NCR1 enhancer RNA. Through these dual mechanisms, NKCLR3 induced a suppressive epigenotype in the NCR1 promoter and suppressed the expression of the NCR1 gene. Thus, the NKCLR3-NCR1 axis identified in this study may serve as a novel target to improve therapeutic intervention of NK cells in tumor immunotherapy.

2025-01-01 | GSE285271 | GEO

NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1)

Project description:NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1)

| PRJNA1200109 | ENA

NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1)

Project description:RNA-Seq reveals that NKCLR3 (NK cytotoxicity-associated long noncoding RNA 3, NONHSAT026854) is differentially expressed in VPA-treated human NK cells. To determine whether it is functionally important in NK cell cytotoxicity, we used a RNA reverse transcription-associated trap sequencing (RAT-Seq) approach to profile the genome-wide binding targets for NKCLR3. This dataset will help study the mechanisms underlying the role of NKCLR3 in NK cell cytotoxicity.

2025-01-01 | GSE284721 | GEO

Ncr1

Project description:Rattus norvegicus Ncr1, natural cytotoxicity triggering receptor 1 [Source:RGD Symbol;Acc:621288], is differentially expressed in 11 experiment(s);

| ENSRNOG00000018458 | ExpressionAtlas

Ncr1

Project description:Rattus norvegicus Ncr1, natural cytotoxicity triggering receptor 1 [Source:RGD Symbol;Acc:621288], is expressed in 2 baseline experiment(s);

| ENSRNOG00000018458 | ExpressionAtlas

NCR1

Project description:Macaca mulatta NCR1, natural cytotoxicity triggering receptor 1 [Source:VGNC Symbol;Acc:VGNC:75065], is expressed in 3 baseline experiment(s);

| ENSMMUG00000004323 | ExpressionAtlas

NCR1

Project description:Homo sapiens NCR1, natural cytotoxicity triggering receptor 1 [Source:HGNC Symbol;Acc:HGNC:6731], is differentially expressed in 64 experiment(s);

| ENSG00000189430 | ExpressionAtlas

NCR1

Project description:Equus caballus NCR1, natural cytotoxicity triggering receptor 1 [Source:VGNC Symbol;Acc:VGNC:20603], is expressed in 1 baseline experiment(s);

| ENSECAG00000013762 | ExpressionAtlas

NCR1

Project description:Homo sapiens NCR1, natural cytotoxicity triggering receptor 1 [Source:HGNC Symbol;Acc:HGNC:6731], is expressed in 25 baseline experiment(s);

| ENSG00000189430 | ExpressionAtlas

NCR1

Project description:Sus scrofa NCR1, natural cytotoxicity triggering receptor 1 [Source:VGNC Symbol;Acc:VGNC:90619], is differentially expressed in 2 experiment(s);

| ENSSSCG00000022675 | ExpressionAtlas

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