Abrogation of MUC5AC Expression Contributes to the Apoptosis and Cell Cycle Arrest of Colon Cancer Cells

Abstract

Deregulated expressions of mucins have been found in various malignancies and play a pivotal role in carcinogenesis. MUC5AC, as a secreted mucin, is reported to be aberrantly expressed during epithelial cancer progression, including colon cancer. However, the mechanisms of the oncoprotein MUC5AC in the initiation of colon cancer requires further investigation. Here, we collected colon cancer tissues (n = 20) and corresponding paracancerous tissues (n = 20) and found that the expression of MUC5AC was significantly elevated in colon cancer tissues when compared with the corresponding paracancerous tissues. Immunofluorescence indicated that all colon cancer cell lines, including HT29, SW620, and the normal human intestinal epithelial cells FHC, showed the positive expression of MUC5AC, and SW620 exhibited the highest expression. Moreover, knockdown of MUC5AC in SW620 cells remarkably suppressed cell vitality and promoted apoptosis and G1 cell cycle arrest, resulting in the impaired ability of colony formation. Furthermore, the inhibition of MUC5AC in SW620 cells dramatically repressed the cell migration and invasion. These results demonstrated that MUC5AC as an oncogene could be a promising target in the treatment of colon cancer.

MUC1 and MUC5AC implication in Tunisian colorectal cancer patients

“…Our results highlighted that MUC1 and MUC5AC mRNA and protein levels were notably up-regulated in tumor tissues when compared with the normal mucosa. A similar pattern was found in many other studies [2,10,15,23].…”

“…In normal physiological conditions, secretory mucin MUC5AC is not expressed in the colonic mucosa, whereas its aberrant expression is observed during development of colon cancer [1,13,15,23,30].…”

“…This advocates that MUC5AC presence can be a prognostic factor for non-aggressive colorectal carcinomas and a promising target in the treatment of colon cancer [23].…”

Ramifications of secreted mucin MUC5AC in malignant journey: a holistic view

“…The genetic inhibition of MUC5AC in colon cancer cells impaired the colony-forming ability of these cells by reducing cell viability, increased apoptosis and G 1 cell cycle arrest. Interestingly, loss of MUC5AC dramatically repressed the cell migration and invasion of colon cancer cells (182).…”

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

“…Unlike MUC2, the expression of MUC5AC can be found to different degrees during the development of CRC, specifically both in mucinous and nonmucinous adenocarcinomas. Using siRNA technology, Zhu et al knockdown the expression of MUC5AC in SW620 cells, a CRC cell line with high MUC5AC expression, and found that siMUC5AC significantly inhibited cell migration and invasion and induces cell apoptosis and G1-phase cell cycle arrest; these effects resulted in impaired colony formation (Zhu et al, 2016), suggesting that MUC5AC is a promising target for the treatment of colon cancer. Unsurprisingly, CRC patients with high MUC5 expression showed poor cell differentiation, a high lymph node metastasis rate and late stage CRC (Wang et al, 2017), which suggests that MUC5AC is a promoter of tumors.…”