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
Department of Medicine (DIMED), University of Padua, Padua, Italy.
Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Transl Oncol. 2019 Feb;12(2):282-291. doi: 10.1016/j.tranon.2018.10.013. Epub 2018 Nov 16.
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.
miR-224最近已成为散发性结直肠癌发生过程中的驱动性致癌miRNA，但它的致病作用仍存在争议。通过qRT-PCR和原位杂交技术，对一系列具有大量表型和分子特征的侵袭前和侵袭性结直肠病变进行了miR-224表达情况的研究。同时评估了半胱天冬酶-3和半胱天冬酶-7的状态，并将其与miR-224失调相关联。在腺瘤-癌序列以及炎症性肠病发育异常病变中，miR-224显著上调，而在BRAF突变肿瘤以及存在DNA错配修复缺陷的情况下，其表达显著下调。在结直肠癌中，miR-224靶向作用于半胱天冬酶-3和半胱天冬酶-7，并且这种反向关系在肠黏膜转化的最早阶段就已明显。对于BRAF突变/DNA错配修复缺陷肿瘤的创新生物标志物/治疗方法而言，miR-224/半胱天冬酶轴可能代表了一个有趣的研究领域。
