Abstract
NUT midline carcinoma (NMC) is a very aggressive and lethal type of squamous epithelial cell cancer caused due to fusion of BRD4 and NUT genes. The gene fusion results into a new fusion protein that promotes oncogenesis. The detailed molecular mechanisms underlying the NMC are still not clear and new findings are urgently required to complement the current efforts. Abnormal microRNAs (miRNA) expression promotes tumour formation by modulating the functional expression of critical genes other than the parent genes involved in tumour cell proliferation or survival. Here, using Insilco methods, miRNA targeting the transcripts of parent genes (BRD4 and NUT) and the BRD4-NUT fusion gene were predicted. We investigated a situation, wherein abnormal miRNA expression in malignant cells could arise due to deletion and fusion of genomic regions encompassing the target site of miRNA genes. A set of 48 dysregulated miRNAs targeting the critical genes other than the parent genes (BRD4 and NUT) was identified. Functional enrichment analysis of KEGG pathways of target genes of these Ex-miRNAs implicates their role in cancer pathways. Amplification in the expression level of these miRNAs can be used for NMC diagnosis and prognosis.
Highlights
NUT midline carcinoma (NMC) is a fatal form of undifferentiated epithelial cancer affecting both children and adults [1]
We have idetified the miRNA targeting the transcripts of parent genes (BRD4 and NUT) and the BRD4-NUT fusion gene
We hypothesize that some of the miRNAs regulating their respective BRD4 and NUT gene expression may not be required after the BRD4-NUT gene fusion, as the regions targeted by these miRNAs are deleted
Summary
NUT midline carcinoma (NMC) is a fatal form of undifferentiated epithelial cancer affecting both children and adults [1]. We have idetified the miRNA targeting the transcripts of parent genes (BRD4 and NUT) and the BRD4-NUT fusion gene. We hypothesize that some of the miRNAs regulating their respective BRD4 and NUT gene expression may not be required after the BRD4-NUT gene fusion, as the regions targeted by these miRNAs are deleted.
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