In the current study, we found that ZC3H13 was served as a tumor suppressor in CRC cells, which decreased the expression of Snail, Cyclin D1, and Cyclin E1, and increased the expression of Occludin and Zo-1 through inactivating Ras-ERK signaling pathway.
Occludin protein expression level was not significantly correlated with the age (P > 0.05), tumor size (P > 0.05), International Federation of Gynecology and Obstetrics staging (P > 0.05), pathological grades (P > 0.05), and lymph node metastasis (P > 0.05) of the patients.
Collectively, our findings for the first time identify the role of occludin as a tumor promoter and a pro‑metastatic factor in lung cancer, demonstrating that occludin is a potential prognostic biomarker and therapeutic target in lung cancer.
Expression of claudins 1, 4, 5, 7 and occludin was significantly increased in HCC specimens compared to non-neoplastic liver tissues and normal controls (p<0.001 in each case) Moreover, there was a statistically significant association between low level of claudin-4 and advanced tumor grade (p=0.03).
As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.
Occludin is the first discovered constituent of the epithelial tight junction; in recent years, a functional role of occludin as a tumor suppressor has begun to emerge.
HCCs and metastases are characterized by markedly different protein expression pattern of occludin and ZO-1, which phenomenon might be attributed to the different histogenesis of these tumors.
Our results show the functional diversity of occludin and suggest that methylator phenotype of occludin provides enhanced tumorigenic, invasive, and metastatic properties of cancer cells, identifying occludin as a likely candidate for a tumor-suppressor gene in certain types of cancer.
Interestingly, forced expression of an occludin mutant lacking the second extracellular loop did not rescue the epithelial phenotype in vitro nor did it prevent tumor growth in vivo.
Under-expression of the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular abnormalities responsible for the increased permeability of tumour endothelial tight junctions.