Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify ten different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p, which is aberrant in genetically-modified mouse enteroids and human colonoids irrespective of mutational context, is a master regulator of gene expression in CRC. In follow-up experiments, we also demonstrate that miR-24 promotes CRC cell survival. These findings offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.
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The categories of this paper are: systems
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The categories of this paper are: genetics
6
The categories of this paper are: plant
14
The categories of this paper are: biophysics
1
The categories of this paper are: bioinformatics
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The categories of this paper are: immunology
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The categories of this paper are: animal
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The categories of this paper are: molecular
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The categories of this paper are: cell
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The categories of this paper are: cognition
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The categories of this paper are: behavior
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The categories of this paper are: pharmacology
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The categories of this paper are: bioengineering
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The categories of this paper are: pathology
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The categories of this paper are: neuroscience
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The categories of this paper are: biochemistry