Long non-coding RNA ELDR promotes cell cycle progression in normal oral keratinocytes through induction of a CTCF-FOXM1-AURKA signaling axis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816974 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18354368_1.fastq.gz | Fastqsanger.gz | |||
| SRR18354368_2.fastq.gz | Fastqsanger.gz | |||
| SRR18354369_1.fastq.gz | Fastqsanger.gz | |||
| SRR18354369_2.fastq.gz | Fastqsanger.gz | |||
| SRR18354370_1.fastq.gz | Fastqsanger.gz |
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Project description:Long non-coding RNAs (lncRNAs) have gained widespread attention as a potential new layer of regulation in biological processes during development and disease. The lncRNA ELDR (EGFR long non‐coding downstream RNA) was recently shown to be highly expressed in oral cancers as compared to adjacent non-tumor tissue, and we previously reported that ELDR may be an oncogene as inhibition of ELDR reduces tumor growth in oral cancer models. Furthermore, overexpression of ELDR induces proliferation and colony formation in normal oral keratinocytes (NOKs). In this study, we examined in further detail how ELDR drives the neoplastic transformation of normal keratinocytes. We performed RNA-seq analysis on NOKs stably expressing ELDR (NOK-ELDR), which revealed that ELDR enhances the expression of cell cycle-related genes. Increased expression of Aurora kinase A (AURKA) and its downstream gene targets Polo-Like Kinase 1 (PLK1), Cell Division Cycle 25C (CDC25C), Cyclin-Dependent Kinase 1 (CDK1), and Cyclin B1 (CCNB1) are significantly increased in NOK-ELDR cells, suggesting induction of G2/M progression. We further identified CCCTC-Binding Factor (CTCF) as a binding partner of ELDR in NOK-ELDR cells. We showed that ELDR stabilizes CTCF and increases its expression. Finally, we demonstrate the ELDR-CTCF axis upregulates transcription factor Forkhead Box M1 (FOXM1), which induces AURKA expression and downstream G2/M transition. These findings provide mechanistic insights into the role of the lncRNA ELDR as a potential driver of oral cancer during neoplastic transformation of normal keratinocytes.
2022-05-11 | GSE198818 | GEO
Project description:Long noncoding RNAs (lncRNAs) have gained widespread attention as a new layer of regulation in biological processes during development and disease. The lncRNA ELDR (EGFR long noncoding downstream RNA) was recently shown to be highly expressed in oral cancers as compared to adjacent nontumor tissue, and we previously reported that ELDR may be an oncogene as inhibition of ELDR reduces tumor growth in oral cancer models. Furthermore, overexpression of ELDR induces proliferation and colony formation in normal oral keratinocytes (NOKs). In this study, we examined in further detail how ELDR drives the neoplastic transformation of normal keratinocytes. We performed RNA-seq analysis on NOKs stably expressing ELDR (NOK-ELDR), which revealed that ELDR enhances the expression of cell cycle-related genes. Expression of Aurora kinase A and its downstream targets Polo-like kinase 1, cell division cycle 25C, cyclin-dependent kinase 1, and cyclin B1 (CCNB1) are significantly increased in NOK-ELDR cells, suggesting induction of G2/M progression. We further identified CCCTC-binding factor (CTCF) as a binding partner of ELDR in NOK-ELDR cells. We show that ELDR stabilizes CTCF and increases its expression. Finally, we demonstrate the ELDR-CTCF axis upregulates transcription factor Forkhead box M1, which induces Aurora kinase A expression and downstream G2/M transition. These findings provide mechanistic insights into the role of the lncRNA ELDR as a potential driver of oral cancer during neoplastic transformation of normal keratinocytes.
| S-EPMC9079251 | biostudies-literature
Project description:Genome-wide 10k SNP profiling of FOXM1B-transduced N/TERT and primary normal human epidermal keratinocytes (NHEK). The aim of this study was to study the cancer initiation role of UVB and FOXM1B upregulation in NHEK. Upregulation of FOXM1B alone (without UVB) was found to directly induce genomic instability in the form of copy number aberration (CNA) and low levels of loss of heterozygosity (LOH) in primary NHEK. The FOXM1B-induced CNA was found to be retained and accumulated in subsequent cell culture passages. UVB-exposure resulted in significant chromosomal LOH and CNA in N/TERT cells expressing FOXM1B but not in EGFP-expressing cells. This indicates that UVB corroborated with FOXM1B to recruit LOH and CNA which may predispose cell to malignant transformation. Collectively, these results indicate that aberrant upregulation of FOXM1B in skin keratinocytes following UVB exposure may be an early mechanism whereby cells acquire genomic changes required for oncogenesis. Keywords: Genome-wide SNP profiling for loss of heterozygosity (LOH) and copy number aberration (CNA), FOXM1, UVB, Keratinocytes, Basal cell carcinoma, genomic instability, carcinogenesis, squamous cell carcinoma.
2010-06-28 | GSE16937 | GEO
Project description:Genome-wide 10k SNP profiling of FOXM1B-transduced N/TERT and primary normal human epidermal keratinocytes (NHEK). The aim of this study was to study the cancer initiation role of UVB and FOXM1B upregulation in NHEK. Upregulation of FOXM1B alone (without UVB) was found to directly induce genomic instability in the form of copy number aberration (CNA) and low levels of loss of heterozygosity (LOH) in primary NHEK. The FOXM1B-induced CNA was found to be retained and accumulated in subsequent cell culture passages. UVB-exposure resulted in significant chromosomal LOH and CNA in N/TERT cells expressing FOXM1B but not in EGFP-expressing cells. This indicates that UVB corroborated with FOXM1B to recruit LOH and CNA which may predispose cell to malignant transformation. Collectively, these results indicate that aberrant upregulation of FOXM1B in skin keratinocytes following UVB exposure may be an early mechanism whereby cells acquire genomic changes required for oncogenesis. Keywords: Genome-wide SNP profiling for loss of heterozygosity (LOH) and copy number aberration (CNA), FOXM1, UVB, Keratinocytes, Basal cell carcinoma, genomic instability, carcinogenesis, squamous cell carcinoma. 1) Three individual normal primary NHEK cultures were retrovirally transduced (with either EGFP or EGFP-FOXM1B) and left to grow for 4 days prior to SNP array analysis. 2) EGFP or EGFP-FOXM1B-tansduced NHEK cells were harvested at passage 1, 2 and 3 for SNP array analysis to investigate if genomic instability is maintained and accumulated in subsequent passages. 3) N/TERT cells transduced with either EGFP or EFOX were UVB-irradiated and left to grow for 50 days in culture prior to SNP array analysis.
2010-07-29 | E-GEOD-16937 | biostudies-arrayexpress
Project description:Aberrant upregulation of a single oncogene FOXM1 in primary normal human oral epithelial cells orchestrated a cancer-like methylome landscape This study have identified a unique FOXM1-induced epigenetic signature which may have potentials as biomarkers for early oral cancer screening, diagnostic and/or therapeutic interventions Comparisons of primary human normal oral keratinocytes transduced with either EGFP (control) or FOXM1B and a head and neck squamous cell carcinoma cell line SCC15
2012-04-18 | E-GEOD-31767 | biostudies-arrayexpress
Project description:Purpose: AURKA plays an important role in breast cancer development. Exploring the gene expression profiles regulated by AURKA will facilitate to understand the mechanism which is responsible for AURKA induced breast cancer development. Results: We found that 350 genes were significantly up-regulated during AURKA overexpression in MCF-10A cells, 346 genes were significantly down-regulated during AURKA overexpression in MCF-10A cells. Conclusions: Our study indicated that 696 differentially expressed genes might contribute to AURKA induced breast cancer development. MCF-10A cells overexpressed AURKA or the empty vector were subjected to RNA extraction. The resulted RNA samples were performed RNA-sequencing analyses of gene expression profiles.
2015-10-28 | E-GEOD-57931 | biostudies-arrayexpress
Project description:Purpose: AURKA plays an important role in breast cancer development. Exploring the gene expression profiles regulated by AURKA will facilitate to understand the mechanism which is responsible for AURKA induced breast cancer development. Results: We found that 350 genes were significantly up-regulated during AURKA overexpression in MCF-10A cells, 346 genes were significantly down-regulated during AURKA overexpression in MCF-10A cells. Conclusions: Our study indicated that 696 differentially expressed genes might contribute to AURKA induced breast cancer development.
2015-10-28 | GSE57931 | GEO
Project description:Here we integrated multi-omics profiles including transcriptomics, DNA accessibility and capture Hi-C data to explore how p63 shapes local chromatin architecture in skin keratinocytes isolated from EEC syndrome patients. Surprisingly, we observed decreased chromatin accessibility in a number of DNA looping nodes which were co-mediated by p63 and CTCF. Our findings not only identified a new aspect of the bookmark function of p63, but also shed light on the disease mechanism underlined p63 dysfunction. Therefore, we propose p63 as a spatial genome organizer by modulating a subset of DNA loops with CTCF and therefore fine-tuning transcription programs required for skin keratinocytes.
2019-06-21 | GSE123711 | GEO
Project description:To gain insight into genes regulated by AURKA, AURKA was knocked down (KD) in MDA-MB-231 cells
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Project description:IMR-32 cells were infected either with control-shRNA or one of two different AURKA-shRNA vectors to identify genes regulated after AURKA knockdown.
2008-06-01 | E-MEXP-1496 | biostudies-arrayexpress