let-7 microRNAs in development, stem cells and cancer

Trends Mol Med. 2008 Sep;14(9):400-9. doi: 10.1016/j.molmed.2008.07.001. Epub 2008 Jul 31.


MicroRNAs (miRNAs) are small noncoding RNAs, approximately 22 nucleotides in length, that repress target messenger RNAs (mRNAs) through an antisense mechanism. The let-7 miRNA was originally discovered in the nematode Caenorhabditis elegans, where it regulates cell proliferation and differentiation, but subsequent work has shown that both its sequence and its function are highly conserved in mammals. Recent results have now linked decreased let-7 expression to increased tumorigenicity and poor patient prognosis. Moreover, during normal development, accumulation of let-7 can be prevented by LIN28, a promoter of pluripotency. Based on these findings, we propose that let-7 regulates 'stemness' by repressing self-renewal and promoting differentiation in both normal development and cancer. A more complete understanding of its function will thus provide insights into these processes and might yield diagnostic and therapeutic advances for cancer treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasms / diagnosis
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oncogenes
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Transcription, Genetic


  • MicroRNAs
  • let-7 microRNA, C elegans