Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells

Int J Oncol. 2013 Jul;43(1):63-71. doi: 10.3892/ijo.2013.1935. Epub 2013 May 13.


Small and large non-coding RNAs (ncRNAs) contribute to the acquisition of aggressive tumor behavior in diverse human malignancies. Two types of ncRNAs, miRNA‑10b (miR-10b) and homemobox (HOX) transcript antisense RNA (HOTAIR), can suppress the translation of the HOXD10 gene, an mRNA encoding a transcriptional repressor that inhibits the expression of cell migration/invasion-associated genes. Using epithelial ovarian cancer cell lines and primary tumors, we investigated whether miR‑10b and/or HOTAIR can regulate the expression of HOXD10, and whether it permits gain of pro‑metastatic gene products, matrix metallopeptidase 14 (MMP14) and ras homolog family member C (RHOC). Overexpression of miR-10b induced a decrease in HOXD10 protein expression, and upregulated the migration and invasion abilities in ovarian cancer cell lines (P<0.05). In these cells, a significant increase of MMP14 and RHOC protein was observed. No significant upregulation of the HOXD10 protein was observed in cells with the treatment of HOTAIR-siRNA. Positive signals for HOXD10 and MMP14 proteins were observed in 47 (69%) and 25 (37%) of 68 patients with epithelial ovarian cancers. An inverse correlation between HOXD10 and MMP14 immunoreactivities was observed (P<0.05), and miR-10b expression was also inversely correlated with HOXD10 protein expression (P<0.05). These results suggested that downregulation of HOXD10 expression by miR-10b overexpression may induce an increase of pro-metastatic gene products, such as MMP14 and RHOC, and contribute to the acquisition of metastatic phenotypes in epithelial ovarian cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Matrix Metalloproteinase 14 / metabolism*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • rho GTP-Binding Proteins / metabolism*
  • rhoC GTP-Binding Protein


  • Homeodomain Proteins
  • MIRN10 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • HOXD10 protein, human
  • MMP14 protein, human
  • Matrix Metalloproteinase 14
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein