Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long noncoding RNA lnc-H2AFV-1 promotes cell growth by regulating aberrant m6A RNA modification in head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor in the oral and maxillofacial regions, and long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of HNSCC. The lncRNA lnc-H2AFV-1 was found to be upregulated in HNSCC tissues; however, the function of lnc-H2AFV-1 in regulating HNSCC proliferation and the potential molecular mechanism is unclear. The present study evaluated the expression of lnc-H2AFV-1 in HNSCC tissues using quantitative real-time PCR (qPCR) and associated abundant lnc-H2AFV-1 expression with tumor size. Functionally, lnc-H2AFV-1 significantly promoted the proliferation of HNSCC cells in vitro and in vivo. Quantified N6-methyladenosine (m6A) RNA methylation and dot blot assays revealed that total m6A methylation in HNSCC cells was accompanied by lnc-H2AFV-1 expression. Western blotting showed that the expression of methyltransferase-like (METTL) 3 and METTL14 was consistent with that of lnc-H2AFV-1, whereas the expression of demethylase fat mass and obesity-associated (FTO) was contrary to that of lnc-H2AFV-1. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-qPCR revealed that lnc-H2AFV-1 overexpression led to the elevated expression and maximal m6A methylation of intraflagellar transport (IFT) 80 in HNSCC. In addition, METTL3/14 knockdown decreased IFT80 expression. Thus, our findings suggested that lnc-H2AFV-1 might be a biomarker that alters m6A modification by regulating the m6A methylases METTL3/14 and FTO and then mediating the downstream target IFT80 to promote HNSCC progression.

SUBMITTER: Chen X

PROVIDER: S-EPMC9207353 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Long noncoding RNA lnc-H2AFV-1 promotes cell growth by regulating aberrant N6-methyladenosine RNA modification in head and neck squamous cell carcinoma

Project description:Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor in the oral and maxillofacial regions, and long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of HNSCC. in our study, quantified m6A RNA methylation and dot blot assays revealed that total m6A methylation in HNSCC cells was accompanied by lnc-H2AFV-1 expression. Western blotting showed that the expression of methyltransferase-like 3 (METTL3) and 14 (METTL14) was consistent with that of lnc-H2AFV-1, whereas the expression of demethylase fat mass and obesity-associated (FTO) was contrary to that of lnc-H2AFV-1. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-qPCR were used to determined the target genes regulated by lnc-H2AFV-1 overexpression in HNSCC cells.

2022-06-29 | GSE196769 | GEO

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression.

Project description:BackgroundN6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC).MethodsThe prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo.ResultsM6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression.ConclusionsMETTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.

| S-EPMC8919647 | biostudies-literature

The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients.

Project description:RNA methylation at the nitrogen sixth of adenosine (m6A, N6-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m6A modification has been assigned to mediate the biological processes of cancer cells, but their significance in HNSCC development is still poorly described. Thus, the main aim of this study was to globally quantify m6A modification by the mass spectrometry approach and determine the mRNA expression level of selected m6A RNA methyltransferase (METTL3), demethylase (FTO), and m6A readers (YTHDF2, YTHDC2) in 45 HNSCC patients and 4 cell lines (FaDu, Detroit 562, A-253 and SCC-15) using qPCR. In the results, we have not observed differences in the global amount of m6A modification and the mRNA level of the selected genes between the cancerous and paired-matched histopathologically unchanged tissues from 45 HNSCC patients. However, we have found a positive correlation between selected RNA methylation machinery genes expression and m6A abundance on total RNA and characterized the transcript level of those genes in the HNSCC cell lines. Moreover, the lack of global m6A differences between cancerous and histopathologically unchanged tissues suggests that m6A alterations in specific RNA sites may specifically influence HNSCC tumorigenesis.

| S-EPMC8235215 | biostudies-literature

Long Noncoding RNA LINC00460 Promotes Cell Progression by Sponging miR-4443 in Head and Neck Squamous Cell Carcinoma.

Project description:Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. Long noncoding RNAs were proved to be associated with the development and progression in HNSCC. However, the mechanism of LINC00460 in HNSCC needs to be further investigated. The study used quantitative real-time polymerase chain reaction assay to detect the expression of LINC00460 in cancer tissues and cell lines. Gain and loss of function experiments were conducted to analyze the effects of LINC00460 and miR-4443 on cell proliferation, invasion, and apoptosis of HNSCC cells in vitro. The interactions among miR-4443 and LINC00460 were detected by dual-luciferase reporter assay. Here, the study showed that LINC00460 was highly expressed in HNSCC tissues and cell lines. Functionally, knockdown of LINC00460 inhibited HNSCC cell proliferation and migration in vitro. Besides, LINC00460 promoted cell progression by sponging miR-4443, and miR-4443 inhibitor could reverse the effects of si-LINC00460 on cell proliferation and migration. In summary, LINC00460 could potentially promote cell progression and epithelial mesenchymal transition by sponging miR-4443 in HNSCC. LINC00460 could be used as a potential therapeutic target for HNSCCs.

| S-EPMC7563806 | biostudies-literature

Long-Noncoding RNA MANCR is Associated With Head and Neck Squamous Cell Carcinoma Malignant Development and Immune Infiltration.

Project description:Recent studies have demonstrated an important role for mitotically associated long non-coding RNA (MANCR) in carcinogenesis and cancer progression, but its function has not been elucidated in head and neck squamous cell carcinoma (HNSCC). In this study, we identified differentially expressed MANCR from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases across 24 cancer types and included 546 HNSCC patients. Furthermore, high expression of MANCR was verified in HNSCC cell lines and tissue by using real-time quantitative PCR (RT-qPCR) analysis. The Kaplan-Meier analysis showed a worse prognosis with higher levels of MANCR for HNSCC. The univariate Cox regression and multivariate Cox regression analyses revealed that MANCR was a high-risk factor in patients with HNSCC. Thereafter, we carried out the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. It was indicated that MANCR participates in axonogenesis and ECM-receptor interaction. Further enrichment analysis demonstrated that the expression of MANCR was positively correlated with the T gamma delta (tgd) cells, neutrophils, and Th1 cells, and negatively correlated with the infiltration of B cells, CD8 T cells, and T cells in HNSCC. In addition, in vitro experiments showed that knockdown of MANCR in HNSCC cells markedly inhibited cell proliferation, migration, and invasion. We find that MANCR was elevated in HNSCC and promoted the malignant progression of HNSCC. MANCR may serve as a potential biomarker in prognostic implications for HNSCC patients. The positive correlation between MANCR and immune infiltration cells may provide novel therapeutic targets and personalized immune-based cancer therapy for HNSCC.

| S-EPMC9305332 | biostudies-literature

Long noncoding RNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5

Project description:Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. HNSCC cell lines that were sensitive (HN4 and HN30) or resistant (HN4/DDP and HN30/DDP) to cisplatin were used for this study. Moreover, the cisplatin-resistant human melanoma cell lines (A375/DDP) and human lung cancer cell lines (A549/DDP) have also been established. To identify the role of proteins in the acquisition of cisplatin resistance, we analyzed the abnormally expressed protein via protein mass spectrometry methods (isobaric tags for relative and absolute quantitation, iTRAQ) in cisplatin-sensitive and cisplatin-resistant cancer cells, and found that VN1R5 was highly expressed in cisplatin-resistant cells. Long noncoding RNA lnc-POP1-1 upregulated by VN1R5. To deeply investigate the mechanism by which lnc-POP1-1 affects cisplatin resistance in HNSCC cells, we used RNA pull-down assays followed by mass spectrometry to explore the putative RNA-binding proteins (RBPs) interacting with lnc-POP1-1.

2020-11-28 | PXD022799 |

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

m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Cell-Infiltration Characterization in Head and Neck Cancer.

Project description:Background: Recently, RNA modifications have emerged as essential epigenetic regulators of gene expression. However, the mechanism of how RNA N 6-methyladenosine (m6A) modification interacts with tumor microenvironment (TME) infiltration remains obscure. Methods: A total of 876 head and neck cancer samples considering 21 m6A regulators were included and analyzed to determine the m6A modification patterns. These modification patterns were then correlated with TME immune cell-infiltrating characteristics. A scoring system, the m6Ascore, was constructed using principal component analysis algorithms to quantify m6A modification of tumors. Results: Three m6A modification patterns were identified, with TME infiltrating characteristics highly consistent with tumors with three distinct immune phenotypes, including immune-inflamed, immune-exclude, and immune-desert phenotypes. It was demonstrated that the identification of the m6A modification patterns via m6Ascore could predict tumor progression, subtypes, TME stromal activity, variation of relevant genes, and patient prognosis. Low m6Ascore, identified to be an inflamed phenotype, is found to be associated with low stroma activity and tumor mutation burden, high survival probability, increased tumor neoantigen burden, and enhanced response to anti-PD-1/L1 immunotherapy. The therapeutic advantages and clinical benefits of patients with low m6Ascore were further verified in two immunotherapy cohorts. Conclusion: This study identified the significant role that the m6A modification played in the formation of TME characteristics. A more comprehensive understanding of the m6A modification patterns and their correlation with TME infiltration will contribute to the discovery of immunotherapy strategies with better efficacy.

| S-EPMC8859267 | biostudies-literature

Aberrant expression of CPSF1 promotes head and neck squamous cell carcinoma via regulating alternative splicing.

Project description:Alternative mRNA splicing increases protein diversity, and alternative splicing events (ASEs) drive oncogenesis in multiple tumor types. However, the driving alterations that underlie the broad dysregulation of ASEs are incompletely defined. Using head and neck squamous cell carcinoma (HNSCC) as a model, we hypothesized that the genomic alteration of genes associated with the spliceosome may broadly induce ASEs across a broad range of target genes, driving an oncogenic phenotype. We identified 319 spliceosome genes and employed a discovery pipeline to identify 13 candidate spliceosome genes altered in HNSCC using The Cancer Genome Atlas (TCGA) HNSCC data. Phenotypic screens identified amplified and overexpressed CPSF1 as a target gene alteration that was validated in proliferation, colony formation, and apoptosis assays in cell line and xenograft systems as well as in primary HNSCC. We employed knockdown and overexpression assays followed by identification of ASEs regulated by CPSF1 overexpression to identify changes in ASEs, and the expression of these ASEs was validated using RNA from cell line models. Alterations in expression of spliceosome genes, including CPSF1, may contribute to HNSCC by mediating aberrant ASE expression.

| S-EPMC7241804 | biostudies-literature

A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma.

Project description:BackgroundInterferon alpha (IFNα) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains largely unknown.MethodsDifferentially expressed lncRNAs were screened under IFNα stimulation using lncRNA sequencing. The role and mechanism of lncRNA in immunosuppression were investigated in HNSCC in vitro and in vivo.ResultsWe identified a novel IFNα-induced upregulated lncRNA, lncMX1-215, in HNSCC. LncMX1-215 was primarily located in the cell nucleus. Ectopic expression of lncMX1-215 markedly inhibited expression of the IFNα-induced, immunosuppression-related molecules programmed cell death 1 ligand 1 (PD-L1) and galectin-9, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. Binding sites for H3K27 acetylation were found on PD-L1 and galectin-9 promoters. Mechanistically, we found that lncMX1-215 directly interacted with GCN5, a known H3K27 acetylase, to interrupt its binding to H3K27 acetylation. Clinically, negative correlations between lncMX1-215 and PD-L1 and galectin-9 expression were observed. Finally, overexpression of lncMX1-215 suppressed HNSCC proliferation and metastasis capacity in vitro and in vivo.ConclusionsOur results suggest that lncMX1-215 negatively regulates immunosuppression by interrupting GCN5/H3K27ac binding in HNSCC, thus providing novel insights into immune checkpoint blockade treatment.

| S-EPMC6943933 | biostudies-literature

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