Differential MicroRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer

Abstract

One of the most serious complications faced by inflammatory bowel disease (IBD) is the potential development of colorectal cancer (CRC). There is a compelling need to enhance the accuracy of cancer screening of IBD patients. MicroRNAs (miRNAs) are small non-protein-coding RNAs that play important roles in CRC oncogenesis. In this study, we report differential miRNA expression in IBD patients with associated CRC, from non-neoplastic tissue to dysplasia and eventually cancer. In addition, we identify and examine the role of dysregulated miRNAs in the TP53 pathway. In our CD patients, six miRNAs were up-regulated from non-neoplastic tissue to dysplasia, but down-regulated from dysplasia to cancer (miR-122, miR-181a, miR-146b-5p, let-7e, miR-17, miR-143) (p<0.001). Six differentially expressed miRNAs affected the TP53 pathway (miR-122, miR-214, miR-372, miR-15b, let-7e, miR-17) (p<0.001). Using two human colon cancer cell lines (HT-29 and HCT-116), E2F1, an upstream regulator of TP53, was down-regulated in both cell lines transfected with let-7e (p<0.05) as well as in HCT-116 cells transfected with miR-17 (p<0.05). Additionally, cyclin G, a cell-cycle regulator miR-122 target was down-*

Overexpression of Arginine Transporter CAT-1 Is Associated with Accumulation of L-Arginine and Cell Growth in Human Colorectal Cancer Tissue

“…However, colon epithelial cells express very low levels of suppressive miR-122 [41], resulting in higher CAT-1 expression. In CRC cells miR-122 was even down-regulated, indicating a loss of control of CAT-1 expression [42]. Third, although CAT-1 protein on the cellular membrane mediates both influx/efflux and exchange of its substrates, arginine, lysine, and ornithine, between intracellular and extracellular pools, differential expression of CAT-1 protein on the plasma membrane of different organelles within the cells may regulate these amino acid pools in different organelles [32].…”

MicroRNAs miR-146-5p and let-7f as prognostic tools for aggressive papillary thyroid carcinoma: a case report

“…In the last 4 years, several studies have demonstrated the potential of miRNAs in PTC diagnosis. Although miR-146b-5p is down-regulated in other types of cancer (11)(12)(13), this miRNA is highly overexpressed in PTCs (14,15), reliably distinguishing this type of cancer from follicular carcinoma (FTC), and from benign lesions (16,17). Moreover, Schwertheim and cols.…”

miR-214: a potential biomarker and therapeutic for different cancers

“…It was found that miR-214 targets FGFR1 in CRC cells and it was proposed that downregulation of miR-214 is associated with CRC liver metastasis [68]. Another study reported that miR-214 along with other miRNAs was one which altered the p53 pathway and caused CRC [69]. Recent literature has also suggested that downregulation of miR-214 in CRC tissue leads to lung metastasis [70].…”