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Science Forum

Science Forum

  1. 22 Mar '08 12:00
    These are a very interesting new class of gene regulators called microRNAs (miRNAs) and form these beautiful hairpin structures. Big area of research now.
  2. Standard member Thequ1ck
    Fast above
    25 Mar '08 17:34 / 1 edit
    Originally posted by Diodorus Siculus
    These are a very interesting new class of gene regulators called microRNAs (miRNAs) and form these beautiful hairpin structures. Big area of research now.
    That's pretty cool. Could have some important uses in
    treating cancer if the mechanism could be adjusted to
    generate anti-sense mRNA as a site specific inhibitor.
  3. 27 Mar '08 13:26
    Yes precisely and there is some good work looking at miRNA loss leading to metastasis from breast cancer to bone and lung. Anti-microRNAs targeted to viruses have also shown some promise. Below is the conclusions from a recent paper by Tavazoie et al. Nature 2008:
    Endogenous human microRNAs that suppress breast cancer metastasis

    Multiple lines of evidence provided here argue for the involvement of specific miRNAs in suppressing breast cancer metastasis. miR-335, miR-206 and miR-126 are selectively downregulated across a number of highly metastatic human cell lines compared to the general tumour cell population and have demonstrated abilities to suppress metastasis of breast cancer cells to different organ sites. The expression of miR-335 and miR-126 in human mammary tumours is inversely associated with metastatic relapse of these tumours to distant organs, and the expression of miR-206 also shows a trend in the same direction. The expression of a set of genes regulated by one of these miRNAs, miR-335, is directly associated with relapse. We also establish two of these genes, SOX4 and TNC, as in vivo mediators of metastasis. The role of SOX4 in haematopoietic progenitor development suggests that its transcriptional programme may be re-used not only for cancer cell invasion in cooperation with tenascin C but also for tumour initiation in the metastatic niche. miR-335 and miR-126 are expressed in normal human breast tissue. Our findings on their roles in the pathogenesis of human breast cancer argue for an important function for these regulators in maintaining normal tissue integrity. Recently, miR-10b was identified as a miRNA whose overexpression in breast cancer cells promoted tumour growth and lung micrometastasis. Our work expands on this by identifying miRNAs as clinically meaningful suppressors of metastasis. MicroRNAs are thus uncovered as another class of molecules, along with metastasis suppressor genes, that negatively regulate tumour progression.

    The recent implication of miRNAs and miRNA processing in tumorigenesis has raised interest in identifying the specific miRNAs for which loss of expression enhances tumorigenesis, the mechanisms by which they act, and the phenotypic advantages afforded to cells that lose miRNA expression. Our findings suggest that within a tumour, the loss of specific miRNAs provides a selective advantage for cells destined for metastatic colonization. A global downregulation of miRNAs in cancer may serve metastasis by reducing the threshold for loss of specific miRNAs in a subset of cells that will ultimately metastasize. That one such miRNA (miR-335) regulates a set of putative, and a subset of validated, metastasis genes argues that the multi-gene regulatory capacity of a miRNA can function as a barrier to tumour progression in humans. The strong association of the loss of miR-335 and miR-126 expression with metastatic relapse suggests the potential for the use of these molecules in prognostic stratification of breast cancer patients in addition to conventional clinical and pathological staging markers.