@article {1503167,
	title = {miR-155 drives oncogenesis by promoting and cooperating with mutations in the c-Kit oncogene},
	journal = {Oncogene},
	volume = {38},
	number = {12},
	year = {2019},
	month = {2019 03},
	pages = {2151-2161},
	abstract = {MicroRNAs (miRNAs) have emerged as crucial players in the development and maintenance of disease. miR-155 is an inflammation-associated, oncogenic miRNA, frequently overexpressed in hematological malignancies and solid tumors. However, the mechanism of oncogenesis by miR-155 is not well characterized, and research has focused primarily on individual, direct targets, which does not recapitulate the complexities of cancer. Using a powerful, inducible transgenic mouse model that overexpresses miR-155 and develops miR-155-addicted hematological malignancy, we describe here a multi-step process of oncogenesis by miR-155, which involves cooperation between miR-155, its direct targets, and other oncogenes. miR-155 is known to target DNA-repair proteins, leading to a mutator phenotype, and we find that over 93\% of tumors in our miR-155 overexpressing mice contain activating mutations in a single oncogene, c-Kit. Treating mice with dasatinib or imatinib, which target c-Kit, resulted in complete tumor regression, indicating that c-Kit activity is crucial in the oncogenic process. Interestingly, c-Kit expression is high when miR-155 is overexpressed, indicating further cooperation between miR-155 and c-Kit. Our findings support a multi-step model of oncogenesis by miR-155 in which miR-155 promotes both a mutator phenotype and a cellular environment particularly susceptible to mutations in a given oncogene.},
	keywords = {Animals, Carcinogenesis, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Mice, MicroRNAs, Mutation, Oncogenes, Proto-Oncogene Proteins c-kit},
	issn = {1476-5594},
	doi = {10.1038/s41388-018-0571-y},
	author = {Witten, Lisa W and Cheng, Christopher J and Slack, Frank J}
}
