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Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma [miRNA-Seq]

ABSTRACT: Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma [miRNA-Seq]

PROVIDER: PRJNA1026481 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26332694.fastq.gz	Fastqsanger.gz
	SRR26332695.fastq.gz	Fastqsanger.gz
	SRR26332696.fastq.gz	Fastqsanger.gz
	SRR26332697.fastq.gz	Fastqsanger.gz
	SRR26332698.fastq.gz	Fastqsanger.gz

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Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma [ChIRP-seq]

Project description:Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) during target therapy. Yet the mechanism that caused cetuximab resistance, especially the miRNA regulation therein remains unclear. With growing evidence suggests that miRNAs may function within the cell nucleus and act as “nuclear activating miRNAs” for targeting the promoter region or enhancers related to target genes. They are believed to regulate diseases development including tumorigenesis. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, qRT-PCR and FISH results provide compelling evidence of miR-451a nuclear enrichment with cetuximab treatment. ChIRP-seq, microarray, bioinformatic analysis and dual luciferase reporter assay results show that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It is also demonstrated that activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Analyses of HNSCC samples through logistic regression indicated the significance of miR-451a and KDM7A in cetuximab resistance. These discoveries hold promise for the potential utilization of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear activating miRNAs.

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Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma [miRNA-Seq]

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Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma

Project description:Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma

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Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma [ChIRP-seq]

Project description:Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma [ChIRP-seq]

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Nuclear activating miR-451a induced cetuximab resistance in HNSCC [microarray]

Project description:To filter the up-regulated gene induced by miR-451a overexpression and in cetuximab resistant HNSCC cell. We employed whole genome microarray. The HNSCC cell CAL27 was used as a control sample. CAL27_CTX, the cetuximab resistant CAL27 was compared with CAL27. The miR-451a overexpressed CAL27_451a sample was compared with the CAL27_NC sample. CAL27_CTX and CAL27_451A samples were collected after 48h of cetuximab treatment. The microarray results were taken together with ChIRP-seq analysis and bioinformatics analysis for miR-451a binding and enhancer analysis to eventually find the nuclear acticating target of miR-451a

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Cetuximab resistant or sensitive head and neck cancer samples

Project description:10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant. YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer. head and neck cancer cell lines with established cetuximab response were selected. 5 cetuximab resistant cell lines and 5 cetuximab sensitive cell lines were selected for gene genome wide gene copy number analysis on the Affymetrix SNP6.0 array

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Cetuximab resistant or sensitive head and neck cancer samples

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Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

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Regulation of HB-EGF by miR-212 and acquired cetuximab-resistance in head and neck cancer

Project description:To determine the mechanism of cetuximab-resistance in head and neck cancer, a cetuximab-sensitive cell line (SCC1) and its cetuximab-resistant derivative (1Cc8) were analyzed for differentially expressed genes using DNA microarrays. 900 differentially expressed genes were found using the statistical cut-off point of one-way ANOVA with FDR less than 1%.

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