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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245160 | GEO | 2024/01/01

REPOSITORIES: GEO

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