Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway

J Transl Med. 2014 Sep 8:12:244. doi: 10.1186/s12967-014-0244-8.


Aberrant expression of miR-1 has been implicated in various cancers. However, the mechanisms underlying the role of miR-1 in CRC progression still have not been clarified clearly. Here, we showed the decreased expression of miR-1 in colorectal carcinoma (CRC) tissues and cell lines. Ectopic introduction of miR-1 suppressed cell proliferation and migration, whereas miR-1 inhibitor performed contrary functions in CRC cells. Stable overexpression of miR-1 was sufficient to inhibit tumor growth and homing capacity in vivo. Proteomic analysis revealed that miR-1 modulated the expression of key cellular molecules and involved in the MAPK and PI3K/AKT pathways by inhibiting phosphorylation of ERK and AKT. Meanwhile, miR-1 also reversed epithelial-mesenchymal transition (EMT), which played a pivotal role in the initiation of metastasis. Further studies found that miR-1 can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, identified as a CRC-associated protein. In contrast to the phenotypes induced by miR-1 restoration, LASP1-induced cell proliferation and migration partly rescued miR-1-mediated biological behaviors. Our results illustrated that miR-1 play a critical role in CRC progression, which suggests its potential role in the molecular therapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / genetics*
  • Humans
  • MAP Kinase Signaling System*
  • MicroRNAs / physiology*
  • Neoplasm Metastasis*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*


  • MIRN1 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt