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Abstract: Tumor viruses are a class of pathogens with well established roles in the development of malignant diseases. Numerous bodies of work have highlighted miRNAs (microRNAs) as critical regulators of tumor pathways and it is clear that the dysregulation of cellular miRNA expression can promote tumor formation. Tumor viruses encode their own miRNAs and/or manipulate the expression of cellular miRNAs to modulate their host cell environment, thereby facilitating their respective infection cycles. The modulation of these miRNA responsive pathways, however, often influences certain signal transduction cascades in ways that favor tumorigenesis. In this review, we discuss the roles of virally-encoded and virally-regulated cellular miRNAs in the respective viral life cycles and in virus associated pathogenesis. [Copyright &y& Elsevier]

Abstract: Three-dimensional organotypic culture using reconstituted basement membrane matrix (rBM 3-D) is an invaluable tool to characterize morphogenesis of epithelial cells and to elucidate the tumor-modulating actions of extracellular matrix. microRNAs (miRNA) are a novel class of tumor modulating genes. A substantial amount of investigation of miRNAs in cancer is carried out using monolayer 2-D culture on plastic substratum, which lacks a consideration of the matrix-mediated regulation of miRNAs. In the current study we compared the expression of miRNAs in rBM 3-D and 2-D cultures of two lung adenocarcinoma cell lines. Our findings revealed a profound difference in miRNA profiles between 2-D and rBM 3-D cultures of lung adenocarcinoma cells. The rBM 3-D culture-specific miRNA profile was highlighted with higher expression of the tumor suppressive miRNAs (i.e., miR-200 family) and lower expression of the oncogenic miRNAs (i.e., miR-17–92 cluster and miR-21) than that of 2-D culture. Moreover, the expression pattern of miR-17, miR-21, and miR-200a in rBM 3-D culture correlated with the expression of their targets and acinar morphogenesis, a differentiation behavior of lung epithelial cells in rBM 3-D culture. Over-expression of miR-21 suppressed its target PTEN and disrupted acinar morphogenesis. In summary, we provide the first miRNA profile of lung adenocarcinoma cells in rBM 3-D culture with respect to acinar morphogenesis. These results indicate that rBM 3-D culture is essential to a comprehensive understanding of the miRNA biology in lung epithelial cells pertinent to lung adenocarcinoma. [Copyright &y& Elsevier]