Dataset Information

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

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.

SUBMITTER: Fassan M

PROVIDER: S-EPMC6240712 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Fassan Matteo M Cui Ri R Gasparini Pierluigi P Mescoli Claudia C Guzzardo Vincenza V Vicentini Caterina C Munari Giada G Loupakis Fotios F Lonardi Sara S Braconi Chiara C Scarpa Marco M D'Angelo Edoardo E Pucciarelli Salvatore S Angriman Imerio I Agostini Marco M D'Incá Renata R Farinati Fabio F Gafà Roberta R Lanza Giovanni G Frankel Wendy L WL Croce Carlo Maria CM Valeri Nicola N Rugge Massimo M

Translational oncology 20181116 2

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 th ...[more]

PMID: 30448733

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Project description:Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different alpha(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of type IV collagen (alpha1/alpha 4/alpha 6) and type VII collagen (alpha1) during colorectal cancer carcinogenesis.Using quantitative RT-PCR, we have determined the mRNA levels for alpha1(IV), alpha 4(IV), alpha 6(IV), and alpha1(VII) in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to beta-actin. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients.The alpha1(IV) and alpha1(VII) mRNA levels were statistically significantly higher in colorectal cancer tissue (p < 0.001) as compared to corresponding tissue from healthy controls. This is an early event as tissue from adenomas also displayed a higher level. There were small changes in the levels of alpha 4(IV). The level of alpha 6(IV) was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p < 0.01). The localisation of type IV and type VII collagen was visualized by immunohistochemical staining.Our results suggest that the down-regulation of alpha 6(IV) mRNA coincides with the acquisition of invasive growth properties, whereas alpha1(IV) and alpha1(VII) mRNAs were up-regulated already in dysplastic tissue. There are no differences in collagen expression between tissues from healthy individuals and normal tissues from affected individuals.

Dataset Information

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

Publications

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

Similar Datasets

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