MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)

J Biol Chem. 2007 May 11;282(19):14328-36. doi: 10.1074/jbc.M611393200. Epub 2007 Mar 15.


MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that mir-21 is overexpressed in tumor tissues compared with the matched normal tissues. Moreover, suppression of mir-21 by antisense oligonucleotides inhibits tumor cell growth both in vitro and in vivo. However, it remains largely unclear as to how mir-21 affects tumor growth, because our understanding of mir-21 targets is limited. In this study, we performed two-dimensional differentiation in-gel electrophoresis of tumors treated with anti-mir-21 and identified the tumor suppressor tropomyosin 1 (TPM1) as a potential mir-21 target. In agreement with this, there is a putative mir-21 binding site at the 3'-untranslated region (3'-UTR) of TPM1 variants V1 and V5. Thus, we cloned the 3'-UTR of TPM1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. Moreover, deletion of the mir-21 binding site abolished the effect of mir-21 on the luciferase activity, suggesting that this mir-21 binding site is critical. Western blot with the cloned TPM1-V1 plus the 3'-UTR indicated that TPM1 protein level was also regulated by mir-21, whereas real-time quantitative reverse transcription-PCR revealed no difference at the mRNA level, suggesting translational regulation. Finally, overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth. Thus, down-regulation of TPM1 by mir-21 may explain, at least in part, why suppression of mir-21 can inhibit tumor growth, further supporting the notion that mir-21 functions as an oncogene.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Luciferases
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • Oligonucleotides, Antisense / pharmacology*
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tropomyosin / antagonists & inhibitors
  • Tropomyosin / genetics
  • Tropomyosin / metabolism*
  • Tumor Stem Cell Assay


  • 3' Untranslated Regions
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • TPM1 protein, human
  • Tpm1 protein, mouse
  • Tropomyosin
  • Luciferases