MiR-93 enhances angiogenesis and metastasis by targeting LATS2

Cell Cycle. 2012 Dec 1;11(23):4352-65. doi: 10.4161/cc.22670. Epub 2012 Oct 30.

Abstract

Here we report that miR-93, a miRNA in the miR-106B~25 cluster, a paralog of the miR-17-92 cluster, was significantly upregulated in human breast carcinoma tissues. We stably expressed miR-93 in the MT-1 human breast carcinoma cell line and found that tumors formed by the miR-93 cells contained more blood vessels than those formed by the control cells. Co-culture experiments indicated that the MT-1 cells displayed a high activity of adhesion with endothelial cells and could form larger and more tube-like structures with endothelial cells. Lung metastasis assays were performed in a mouse metastatic model, and it was found that expression of miR-93 promoted tumor cell metastasis to lung tissue. In cell culture, expression of miR-93 enhanced cell survival and invasion. We examined the potential target that mediated miR-93's effects and found that the large tumor suppressor, homology 2 (LATS2) was a target of miR-93. Higher levels of LATS2 were associated with cell death in the tumor mass. Silencing LATS2 expression promoted cell survival, tube formation and invasion, while ectopic expression of LATS2 decreased cell survival and invasion. These findings demonstrated that miR-93 promoted tumor angiogenesis and metastasis by suppressing LATS2 expression. Our results suggest that the inhibition of miR-93 function may be a feasible approach to repress tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Movement
  • Cell Survival
  • Coculture Techniques
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Nude
  • Mice, SCID
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transplantation, Heterologous
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • MIRN93 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases