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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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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

XIAP promotes metastasis of bladder cancer cells by ubiquitylating YTHDC1

Project description:X-linked inhibitor of apoptosis protein (XIAP), a member of the IAP family, is overexpressed in a variety of tumors and plays an important role in tumor progression. Increasing evidence suggests that XIAP promotes metastasis of bladder cancer but the underlying mechanism is not very clear. The RNA N6-methyladenosine (m6A) reader YTHDC1 regulates RNA splicing, nuclear transport, and mRNA stability and is a potential tumor target; however, its ubiquitin E3 ligase has not been described. In this study, screening of proteins that specifically interact with XIAP identified YTHDC1 to be its degradation substrate. Ectopic overexpression of XIAP promoted degradation of YTHDC1, and knockout of XIAP upregulated YTHDC1, which inhibited metastasis of bladder cancer. Furthermore, YTHDC1 reduced expression of matrix metalloproteinase-2 (MMP-2) by destabilizing its mRNA. These experiments revealed that XIAP promotes ubiquitination of YTHDC1, positively regulating expression of MMP-2 and promoting metastasis of bladder cancer. Collectively, these findings demonstrate that XIAP is a critical regulator of YTHDC1 and pinpoint the XIAP/YTHDC1/MMP-2 axis as a promising target for the treatment of bladder cancer.

2025-05-07 | PXD055868 | Pride

Gene expression profiling of mir-1825 alteration in Head and neck squamous cell carcinomas

Project description:Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignant cancer worldwide. To understand the pathogenesis of HNSCC, we investigated the effects of miR-1825 overexpression on tumor formation capacity of head and neck cancer cells in vivo using NUDE mice. We searched for potential targets of miR-1828 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene.

2025-07-23 | GSE211921 | 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

RNA sequencing analyses of human liver cancer cell line HepG2 treated with control shRNA and YTHDC1 knockdown shRNA

Project description:YTHDC1 is one of m6A reader proteins exerting multifaceted effects on determining the fate of m6A RNA within the nucleus.To understand how YTHDC1 contributes to liver cancer progression, we conducted RNA-seq assay in shCtrl and shDC1 HepG2 cells and aimed to identified YTHDC1-responsive genes.

2025-03-25 | E-MTAB-14193 | 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