The prognostic value of microRNA-200 family expression in digestive system tumors: A meta-analysis and validation

The relevance of miR-200 family in the prognosis of digestive system tumors remains controversial. Through a systematic review of the pertinent literature using online databases including PubMed, EMBASE, The Cochrane Library, and Web of Science, our pooled-analysis revealed that miR-200 family downregulation was significantly correlated with poor overall survival (OS, hazard ratio [HR] > 1) and disease-free survival (HR > 1) in digestive malignancies. Consistently, subgroup analyzes of various organ tissues, univariate analysis, gastric cancer, pancreatic cancer, and patients of American descent revealed the hazardous effects of miR-200 family downregulation. In contrast, low miR-200 family expression in blood samples predicted favorable OS (HR < 1). Moreover, lower expression levels of miR-200c-5p and miR-429 were validated in esophageal squamous cell carcinoma (ESCC) tissues. Both the protein and messenger RNA expression levels of Paralemmin-2 (PALM2) and Mitotic Arrest Deficient 2-Like Protein (MAD2L1), regulated by miR-200c-5p, were notably higher in ESCC, and increased protein levels of PALM2 and MAD2L1 were correlated with adverse OS. PALM2 overexpression significantly enhanced ESCC cell migration. In conclusion, our study highlights the prognostic value of miR-200 family in digestive system tumors, and the decrease of miR-200c-5p may promote ESCC invasion through upregulation of PALM2 and MAD2L1.