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miR-224 Is Significantly Upregulated and Targets Caspase-3 and Caspase-7 During Colorectal Carcinogenesis12

miR-224 has recently emerged as a driver oncomiR in sporadic colorectal carcinogenesis, but its pathogenetic role is still controversial. A large phenotypical and molecularly characterized series of preinvasive and invasive colorectal lesions was investigated for miR-224 expression by qRT-PCR and in...

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Published in:Translational oncology 2018-11, Vol.12 (2), p.282-291
Main Authors: Fassan, Matteo, Cui, Ri, Gasparini, Pierluigi, Mescoli, Claudia, Guzzardo, Vincenza, Vicentini, Caterina, Munari, Giada, Loupakis, Fotios, Lonardi, Sara, Braconi, Chiara, Scarpa, Marco, D'Angelo, Edoardo, Pucciarelli, Salvatore, Angriman, Imerio, Agostini, Marco, D'Incá, Renata, Farinati, Fabio, Gafà, Roberta, Lanza, Giovanni, Frankel, Wendy L., Croce, Carlo Maria, Valeri, Nicola, Rugge, Massimo
Format: Article
Language:English
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Summary:miR-224 has recently emerged as a driver oncomiR in sporadic colorectal carcinogenesis, but its pathogenetic role is still controversial. A large phenotypical and molecularly characterized series of preinvasive and invasive colorectal lesions was investigated for miR-224 expression by qRT-PCR and in situ hybridization. The caspase-3 and caspase-7 status was also assessed and correlated to miR-224 dysregulation. miR-224 was significantly upregulated during the adenoma-carcinoma sequence and in the context of inflammatory bowel disease dysplastic lesions, whereas its expression was significantly downregulated among BRAF -mutated tumors and in the presence of a DNA mismatch repair deficiency. miR-224 targets caspase-3 and caspase-7 in colorectal cancer, and this inverse relation was already evident from the earliest phases of transformation in intestinal mucosa. The miR-224/caspases axis may represent an interesting field of study for innovative biomarkers/therapeutics for BRAF -mutated/DNA mismatch repair-deficient tumors.
ISSN:1936-5233
DOI:10.1016/j.tranon.2018.10.013