MicroRNA-21 targets tumor suppressor genes in invasion and metastasis

Cell Res. 2008 Mar;18(3):350-9. doi: 10.1038/cr.2008.24.

Abstract

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 (TPM1). Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 (PDCD4) and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Oncogenes*
  • RNA, Messenger / biosynthesis
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • Serpins / biosynthesis
  • Serpins / genetics
  • Tropomyosin / biosynthesis
  • Tropomyosin / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • SERPIN-B5
  • Serpins
  • TPM1 protein, human
  • Tropomyosin
  • Tumor Suppressor Proteins