Diverse expression patterns of mucin 2 in colorectal cancer indicates its mechanism related to the intestinal mucosal barrier.

BACKGROUND: Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear. AIM: To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC. METHODS: Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ 2 test or Fisher's exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests. RESULTS: Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO (χ 2 = 3.957, P < 0.05) and D-LAC (χ 2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival. CONCLUSION: MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.

The Diverse Roles of the Mucin Gene Cluster Located on Chromosome 11p15.5 in Colorectal Cancer.

Colorectal cancer (CRC), the third most common malignant tumor in the world, shows multiple complex and pathologies based on the impaired structure and function of the intestinal mucosal barrier. Goblet cells secrete mucins, which are involved in the formation of the intestinal mucosal barrier and not only lubricate and protect the intestinal mucosa but also participate in the processes of cell adhesion, intercellular signal transduction, and immune regulation. It is accepted that the disordered expression and dysfunction of mucins are associated with the occurrence and development of CRC. This article focuses on the secretory mucins encoded by a gene cluster located on chromosome 11p15.5 and systematically reviews their composition, regulation, function, and role in CRC, to deepen the understanding of the pathogeneses of CRC and to provide a new basis and ideas for the treatment of CRC.

Overexpression of microRNA-98 inhibits cell proliferation and promotes cell apoptosis via claudin-1 in human colorectal carcinoma.

Colorectal carcinoma (CRC) is a major cause of cancer-related deaths worldwide, and investigations on novel targets are imperative. MiR-98 has been reported to act as a tumor suppressor in several cancers. To evaluate miR-98 as a novel anticancer molecule for CRC, examinations to validate whether miR-98 conferred an inhibiting effect on proliferation, migration, and invasion were performed. The microarray-based gene expression profiling involving CRC was used to identify the differentially expressed genes. The potential relationship between miR-98 and CLDN1 was analyzed by cell experimentation. Then, the CRC cells were transfected with miR-98 mimic or miR-98 inhibitor to investigate the potential effect of miR-98 overexpression and depletion on CRC cell proliferation, migration, invasion, and apoptosis. The expressions of CLDN1, Bcl-2 associated protein x (Bax), runt-related transcription factor 3 (RUNX3), B-cell lymphoma 2 (Bcl-2), C-myc, and proliferating cell nuclear antigen (PCNA) were determined. The downregulated miR-98 along with an upregulated CLDN1 was observed in CRC, in which miR-98 could target to regulate CLDN1. The overexpression of miR-98 or silencing of CLDN1 was shown to increase the expression of Bax and RUNX3 along with promoted cell apoptosis and arrested cells in G1 phase, while decreasing the expression of CLDN1, Bcl-2, C-myc, and PCNA with suppressed proliferation, migration, and invasion. Collectively, the current study supports the notion that miR-98 plays an inhibitory role in human CRC cell proliferation, migration, and invasion and act as a contributor for cell apoptosis by downregulating CLDN1. The current study highlights a potential future strategy to help prevent the development of CRC.