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YTHDC1 promotes stemness maintenance and malignant progression in head and neck squamous cell carcinoma

ABSTRACT: YTHDC1 promotes stemness maintenance and malignant progression in head and neck squamous cell carcinoma

PROVIDER: PRJNA844915 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19523478_1.fastq.gz	Fastqsanger.gz
	SRR19523478_2.fastq.gz	Fastqsanger.gz
	SRR19523479_1.fastq.gz	Fastqsanger.gz
	SRR19523479_2.fastq.gz	Fastqsanger.gz
	SRR19523480_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma.

Project description:BackgroundYTH domain containing 1 (YTHDC1), an N6-methyladenosine (m6A) modification reading protein, plays a key role in regulating RNA translation and degradation. However, the role of YTHDC1 in head and neck squamous cell carcinoma (HNSCC) cancer stem cells remains largely unknown. This study is aimed at investigating the role of YTHDC1 in HNSCC and exploring its role in regulating cancer stem cells.MethodsRNA sequencing was used to detect differentially expressed genes (DEGs) between SCC9 spheres and SCC9 cells and to uncover molecular pathways and target molecules associated with CSCs. We detected YTHDC1 expression in The Cancer Genome Atlas (TCGA) database data and clinical samples. Subsequently, YTHDC1 gene suppression assays were performed in HNSCC cell lines to investigate the effect of YTHDC1 on tumor cell stemness maintenance, proliferation, and migration capacity. To further confirm the role of YTHDC1 in regulating cancer stem cells in HNSCC, we analyzed online HNSCC single-cell transcriptomic data to investigate YTHDC1 expression patterns at the single-cell level and the correlation of these levels with the expression of stem cell markers.ResultsYTHDC1 expression levels were significantly upregulated in SCC9 spheres, and YTHDC1 was aberrantly expressed in HNSCC tumor tissues. The increased YTHDC1 expression was closely correlated with the clinical characteristics of HNSCC patients. YTHDC1 regulates the malignant phenotype of HNSCC in both in vivo and in vitro studies. Further single-cell transcriptomic data analysis revealed that YTHDC1 positively correlated with malignant epithelial cell stemness capacity at the single-cell level, and that YTHDC1 was involved in regulating stemness maintenance in HNSCC.ConclusionsThese findings suggest that YTHDC1 may serve as a biomarker for stem maintenance and malignant progression in HNSCC, providing new insights into the treatment of cancer.

| S-EPMC9675605 | biostudies-literature

YTHDC1 promotes stemness maintenance and malignant progression in head and neck squamous cell carcinoma

Project description:RNA sequencing was used to detect differential expressed genes (DEGs) between SCC9-sphere and SCC9 cell line and to uncover molecular pathways and target molecules associated with cancer stem cells.

2024-06-14 | GSE205380 | GEO

Super-enhancer driven LIF/LIFR-STAT3-SOX2 regulatory feedback loop promotes cancer stemness in head and neck squamous cell carcinoma (ChIP-seq)

Project description:Super-enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identified leukemia inhibitory factor (LIF)-SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer-associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine or paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF-SE recruited SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activated downstream LIFR-STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF-SE-LIF/LIFR-STAT3-SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlated with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma were negatively associated with patient survival and dramatically diminished following cancer eradication. Therapeutically, pharmacological targeting LIF-SE-LIF/LIFR-STAT3 significantly impaired tumor growth and reduced CSC subpopulations in HNSCC xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF-SE-mediated auto-regulatory loop in regulating HNSCC stemness and highlight LIF as a novel non-invasive biomarker and potential therapeutic target for HNSCC.

2024-11-06 | GSE274995 | GEO

Super-enhancer driven LIF/LIFR-STAT3-SOX2 regulatory feedback loop promotes cancer stemness in head and neck squamous cell carcinoma (ATAC-seq)

2024-11-06 | GSE274994 | GEO

DKK3 overexpression increases malignant property in head and neck squamous cell carcinoma-derived HSC-3 cells.

Project description:We hypothesized that DKK3 may exert oncogenic function supecifically in head and neck squamous cell carcinoma (HNSCC). DKK3 overexpression in HNSCC cell resulted in elevated cellular proliferation, migration, invasion and in vivo tumor growth. This elevated malignant properties was not driven by Wnt/beta-catenin pathway.

2017-07-22 | GSE84725 | GEO

Head and neck squamous cell carcinoma

Project description:Quantitative (iTRAQ 4-plex) proteomic analysis of progressive head and neck cancers

2022-03-01 | PXD001438 | Pride

PAR-CLIP analysis of YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 in human HeLa cells

Project description:Label the cells overexpressed Flag tagged YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 with 4-SU, the RNA bound by YTHDC1 and SRSF proteins can be got by Flag IP followed by RNA isolation by using the TRIzol (Invitrogen) reagent by following the company manual.the RNA was then used for library preparation using a TruSeqâ¢ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturerâs protocol.The libraries were sequenced using HiSeq2000 (Illumina) in single-read mode, creating reads with a length of 101 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. Discovery of the binding motif of YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 or SRSF10 in overexpressed Human HeLa cells

2016-02-17 | E-GEOD-71096 | biostudies-arrayexpress

KIF2C is a critical regulator for malignant progression of head and neck squamous cell carcinoma

Project description:KIF2C is a critical regulator for malignant progression of head and neck squamous cell carcinoma

| PRJNA1065903 | ENA

YTHDC1 m6A-dependent and m6A-independent functions converge to preserve DNA damage response (Ythdc1 ChIP-Seq)

Project description:Cells have evolved a robust and highly regulated DNA damage response to preserve their genomic integrity. Although increasing evidence highlights the relevance of RNA regulation, our understanding of its impact on a fully efficient DNA damage response remains limited. Here, through a targeted CRISPR-knockout screen, we identified RNA binding proteins and modifiers that participate in mediating the p53 response. Among the top hits, m6A reader YTHDC1 was identified as a master regulator of p53 expression. YTHDC1 binds to the transcription start sites ofTP53and other genes involved in DNA damage response, promoting their transcriptional elongation. YTHDC1 deficiency leads to reducedTP53expression, and also retention of introns leading to aberrant protein production of key DNA damage factors. While intron retention is dependent on m6A, YTHDC1 favoursTP53transcriptionalpause-release independently of m6A. Depletion of YTHDC1 causes genomic instability and aberrant cancer cell proliferation mediated by genes regulated by YTHDC1. Our results uncover YTHDC1 as an orchestrator of the DNA damage response through distinct mechanisms of co-transcriptional mRNA regulation.

2024-05-07 | GSE239331 | GEO

Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: normal head and neck tissue

Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas. The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 18 normal head and neck samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

2011-10-27 | E-GEOD-25083 | biostudies-arrayexpress

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