https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs), controlling genes involved in cellular processes such as inflammation, cell-cycle regulation, stress response, differentiation, apoptosis, and migration. Thus, miRNAs have been implicated in the regulation of virtually all signaling circuits within a cell, and their dysregulation has been shown to play an essential role in the development and progression of cancer. Here, after a brief description of miRNA genomics, biogenesis, and function, we discuss the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies.

MicroRNAs in cancer.

Initially considered an epiphenomenon, micro ribonucleic acids (also called miRNAs) and other small noncoding RNA molecules are now considered major players in cell biology. MiRNAs regulate gene expression through effects on translation, transcription and chromatin modification. Multiple miRNAs are dysregulated in human cancer and affect the proliferation and apoptosis, metastatic behaviour, invasiveness and phenotype of cancer cells. Virtually every cell type and cancer have a particular expression pattern of miRNA expression. This miRNA profile permits to classify cancer and often gives prognostic information. Profiling based on miRNAs may be more specific and robust than profiling based on mRNAs. MiRNAs can be studied in virtually all tissues including plasma. More work is necessary, but miRNAs have already improved our understanding of the pathogenesis of cancer and appear promising for diagnostic purposes as biomarkers and for the development of new genetic treatments.



Key Concepts: 



MicroRNAs regulate gene expression.




MicroRNAs are important in the pathogenesis and progression of human cancer.




MicroRNAs can function as tumour suppressors and as tumour promoters (oncomirs).




MicroRNAs can serve as biomarkers for cancer and may become useful for the treatment of cancer.






Keywords:

microRNAs;
noncoding RNAs;
gene profiling;
cancer;
leukaemia;
malignancy

MicroRNAs in Cancer

MicroRNAs (miRNAs) are small, noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis. MiRNA expression is deregulated in cancer by a variety of mechanisms including amplification, deletion, mutation, and epigenetic silencing. Several studies have now shown that miRNAs are involved in the initiation and progression of cancer. In this review, we briefly describe miRNA biogenesis and discuss how miRNAs can act as oncogenes and tumor suppressors. We also address the role of miRNAs in the diagnosis, prognosis, and treatment of cancer.

MicroRNAs in Cancer.

https://www.jbc.org/content/283/22/14910.full.pdf

The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2.

MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that are important in many biological processes1,2 Although the oncogenic and tumour-suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumour metastasis was addressed only recently3 and still remains largely unexplored4,5 To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic, human breast tumour cell line that was transduced with a miRNA-expression library and subjected to a trans-well migration assay We found that human miR-373 and miR-520c stimulated cancer cell migration and invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by suppression of CD44 We found significant upregulation of miR-373 in clinical breast cancer metastasis samples that correlated inversely with CD44 expression Taken together, our findings indicate that miRNAs are involved in tumour migration and invasion, and implicate miR-373 and miR-520c as metastasis-promoting miRNAs

The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis

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The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis