RESUMEN
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules of about 22 nucleotides in length. miRNAs are highly conserved in both plants and animals, and function as gene regulators by binding to the 3'-untranslated region of target mRNAs for cleavage and/or translational repression. miRNA biogenesis, stability, and regulation of expression are strongly sequence dependent. Sequence variants, such as single nucleotide polymorphisms (SNPs) in pri-miRNA, pre-miRNA, promoter regions, or miRNA-target sites, can influence miRNA function, thereby contributing to the pathological features of human disease. In this review, we focus on miRNA-related SNPs in gastric cancer and comprehensively analyze some commonly studied SNPs.
Asunto(s)
MicroARNs/genética , Neoplasias Gástricas/genética , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple , ARN Mensajero/genéticaRESUMEN
BACKGROUND: The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis. METHODS: We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC. RESULTS: The results showed that high expression of FOXM1 staining was 85.44% (88/103) in 103 cases of CRC and 20.39% (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines. CONCLUSIONS: Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.