Purpose
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. Since miR-7 regulates the expression of several important drivers of CRC, we analyzed the clinical significance of ciRS-7 in CRC patients.
Experimental Design
Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary CRC tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (n=165), and evaluated the effect of ciRS-7 on miR-7, and its targets genes EGFR and RAF1. Functional analysis were performed in cell lines and an animal model to support clinical findings.
Results
Our data revealed that ciRS-7 was significantly up-regulated in CRC tissues compared with matched normal mucosae (P=0.0018), and its overexpression was associated with poor patient survival (P=0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (P=0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to blocking of tumor suppressive effects of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes.
Conclusions
CiRS-7 is a promising prognostic biomarker in CRC patients and may serve as a therapeutic target for reducingEGFR-RAF1 activity in CRC patients.
Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease, characterized by a combination of symptoms, clinical findings and histological abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients have a solitary ulcer, and the rest of the lesions vary in shape and size, from hyperemic mucosa to broad-based polypoid. Men and women are affected equally, with a small predominance in women. SRUS has also been described in children and in the geriatric population. Clinical features include rectal bleeding, copious mucus discharge, prolonged excessive straining, perineal and abdominal pain, feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This disease has well-described histopathological features such as obliteration of the lamina propria by fibrosis and smooth muscle fibers extending from a thickened muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria and abnormal smooth muscle fiber extensions are sensitive markers for differentiating SRUS from other conditions. However, the etiology remains obscure, and the condition is frequently associated with pelvic floor disorders. SRUS is difficult to treat, and various treatment strategies have been advocated, ranging from conservative management to a variety of surgical procedures. The aim of the present review is to summarize the clinical features, pathophysiology, diagnostic methods and treatment strategies associated with SRUS.
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