Oral cancer overexpressed 1 (ORAOV1): a regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma

Int J Cancer. 2008 Oct 15;123(8):1779-86. doi: 10.1002/ijc.23734.

Abstract

Oral Cancer Overexpressed 1 (ORAOV1) is a novel gene locating at chromosome band 11q13. Recent studies have suggested its role as a candidate oncogene in oral squamous cell carcinoma (OSCC) and its prognostic value for patients with OSCC. Till now, the detailed function of ORAOV1 in OSCC has remained undefined. In this study, we have investigated the role of ORAOV1 in OSCC tumorigenesis by down-regulating its expression. Small interfering RNA (siRNA) has been applied to inhibit the expression of ORAOV1 in OSCC cells. We found that the OSCC cells with reduced ORAOV1 showed retarded cell growth in vitro and displayed inhibition in both tumor growth and tumor angiogenesis in vivo. Further analyses reveal that the retarded cell growth is associated with an increase in apoptosis involving the activation of caspase 3-dependent pathway and a cell cycle arrest at the S-phase with a downregulation of cyclin A, cyclin B1 and cdc2. The suppressed tumor growth in vivo may be attributed to synergistic effect between inhibition in cell growth and suppression of tumor angiogenesis. The latter is most likely because of a suppression of VEGF. Taken together, we demonstrate that ORAOV1 plays pivotal roles in the growth and angiogenesis of OSCC. Thus, ORAOV1 may be a novel target that could be explored to develop therapeutic strategy in OSCC management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carcinoma, Squamous Cell / blood supply*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neovascularization, Pathologic / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • S Phase / physiology
  • Tongue Neoplasms / blood supply*
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology*
  • Transfection

Substances

  • LTO1 protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Small Interfering