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

Matteo Fassan, Ri Cui, Pierluigi Gasparini, Claudia Mescoli, Vincenza Guzzardo, Caterina Vicentini, Giada Munari, Fotios Loupakis, Sara Lonardi, Chiara Braconi, Marco Scarpa, Edoardo D'Angelo, Salvatore Pucciarelli, Imerio Angriman, Marco Agostini, Renata D'Incá, Fabio Farinati, Roberta Gafà, Giovanni Lanza, Wendy L FrankelCarlo Maria Croce, Nicola Valeri, Massimo Rugge

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)282-291
Number of pages10
JournalTranslational Oncology
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2019

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    Fassan, M., Cui, R., Gasparini, P., Mescoli, C., Guzzardo, V., Vicentini, C., Munari, G., Loupakis, F., Lonardi, S., Braconi, C., Scarpa, M., D'Angelo, E., Pucciarelli, S., Angriman, I., Agostini, M., D'Incá, R., Farinati, F., Gafà, R., Lanza, G., ... Rugge, M. (2019). miR-224 Is Significantly Upregulated and Targets Caspase-3 and Caspase-7 During Colorectal Carcinogenesis. Translational Oncology, 12(2), 282-291. https://doi.org/10.1016/j.tranon.2018.10.013