Cancer progression has similarities with the process of epithelial-to-mesenchymal transition (EMT) found during embryonic development, during which cells down-regulate E-cadherin and up-regulate Vimentin expression. By evaluating the expression of 207 microRNAs (miRNAs) in the 60 cell lines of the drug screening panel maintained by the Nation Cancer Institute, we identified the miR-200 miRNA family as an extraordinary marker for cells that express E-cadherin but lack expression of Vimentin. These findings were extended to primary ovarian cancer specimens. miR-200 was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/δEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B). Ectopic expression of miR-200 caused up-regulation of E-cadherin in cancer cell lines and reduced their motility. Conversely, inhibition of miR-200 reduced E-cadherin expression, increased expression of Vimentin, and induced EMT. Our data identify miR-200 as a powerful marker and determining factor of the epithelial phenotype of cancer cells.

/pdf/the-mir-200-family-determines-the-epithelial-phenotype-of-28dubximmp.pdf

The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2

MicroRNAs (miRNAs) are a class of posttranscriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. There are currently over 10,000 miRNAs that have been identified in a range of species including metazoa, mycetozoa, viridiplantae, and viruses, of which 940, to date, are found in humans. It is estimated that more than 60% of human protein-coding genes harbor miRNA target sites in their 3′ untranslated region and, thus, are potentially regulated by these molecules in health and disease. This review will first briefly describe the discovery, structure, and mode of function of miRNAs in mammalian cells, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with our existing knowledge of their targets. Finally, we will summarize some of the advances made in utilizing miRNAs in therapeutics.

/pdf/micrornas-in-development-and-disease-472gt45lvo.pdf

MicroRNAs in development and disease.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.molonc.2012.09.006

MicroRNA and cancer.

Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovaria...

/pdf/the-mammalian-ovary-from-genesis-to-revelation-2e2qokz0h8.pdf

The mammalian ovary from genesis to revelation

Micro (mi)RNAs are small, highly conserved noncoding RNAs that control gene expression post-transcriptionally either via the degradation of target mRNAs or the inhibition of protein translation. Each miRNA is believed to regulate the expression of multiple mRNA targets, and many miRNAs have been linked to the initiation and progression of human cancer. miRNAs control various activities of the immune system and different stages of hematopoietic development, and their misexpression is the cause of various blood malignancies. Certain miRNAs have oncogenic activities, whereas others have the potential to act as tumor suppressors. Because they control fundamental processes such as differentiation, cell growth and cell death, the study of the role of miRNAs in human neoplasms holds great promise for novel forms of therapy. Here, we summarize the role of miRNAs and their targets in contributing to human cancers and their function as regulators of apoptotic pathways and the immune system.

MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death

The microRNA let-7 regulates late embryonic development by suppressing expression of a number of genes such as c-myc and RAS as well as the embryonic gene high mobility group, A2 (HMGA2). We now demonstrate that HMGA2 is more efficiently targeted by let-7 than RAS. Its expression inversely correlates with the expression of let-7 in the NCI60 cells lines, and the expression of RAS does not change when amounts of let-7 that efficiently silence expression of HMGA2 are introduced into tumor cells. We did not find a difference in the expression of HMGA2 between primary ovarian cancer samples and matching metastases, suggesting that the expression of HMGA2 represents an early event during cancer progression. The late repression of HMGA2 by let-7 during embryonic development, and the early reexpression of HMGA2 during cancer development, is in line with the hypothesis that cancer development represents a case of reverse embryogenesis.

Let-7 Prevents Early Cancer Progression by Suppressing Expression of the Embryonic Gene HMGA2

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Let-7 Prevents Early Cancer Progression by Suppressing Expression of the Embryonic Gene HMGA2