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MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. In this study, we demonstrate that miR-214 is frequently down-regulated in cervical cancer, and its expression reduces the proliferation, migration, and invasiveness of cervical cancer cells, whereas inhibiting its expression results in enhanced proliferation, migration, and invasion. miR-214 binds to the 3'-UTR of UDP-N-acetyl-α-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7), thereby repressing GALNT7 expression. Furthermore, we are the first to show, using quantitative real-time PCR, that GALNT7 is frequently up-regulated in cervical cancer. The knockdown of GALNT7 markedly inhibits cervical cancer cell proliferation, migration, and invasion, whereas ectopic expression of GALNT7 significantly enhances these properties, indicating that GALNT7 might function as an oncogene in cervical cancer. The restoration of GALNT7 expression can counteract the effect of miR-214 on cell proliferation, migration, and invasiveness of cervical cancer cells. Together, these results indicate that miR-214 is a new regulator of GALNT7, and both miR- 214 and GALNT7 play important roles in the pathogenesis of cervical cancer. [ABSTRACT FROM AUTHOR]

The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been shown to play important roles in carcinogenesis. However, their underlying mechanisms of action in hepatocellular carcinoma (HCC) are poorly understood. Recent evidence suggests that epigenetic silencing of miRNAs through tumor suppression by CpG island hypermethylation may be a common hallmark of human tumors. Here, we demonstrated that miR-941 was significantly downregulated in HCC tissues and cell lines and was generally hypermethylated in HCC. The overexpression of miR-941 suppressed in vitro cell proliferation, migration, and invasion and inhibited the metastasis of HCC cells in vivo. Furthermore, the histone demethylase KDM6B (lysine (K)-specific demethylase 6B) was identified as a direct target of miR-941 and was negatively regulated by miR-941. The ectopic expression of KDM6B abrogated the phenotypic changes induced by miR-941 inHCCcells. We demonstrated that miR-941 and KDM6B regulated the epithelial- mesenchymal transition process and affected cell migratory/ invasive properties. [ABSTRACT FROM AUTHOR]