A predicted protein, KIAA0247, is a cell cycle modulator in colorectal cancer cells under 5-FU treatment

J Transl Med. 2011 May 28;9:82. doi: 10.1186/1479-5876-9-82.

Abstract

Background: Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and the leading cause of cancer death. The identification of genes related to CRC is important for the development of successful therapies and earlier diagnosis.

Methods: Molecular analysis of feces was evaluated as a potential method for CRC detection. Expression of a predicted protein with unknown function, KIAA0247, was found in feces evaluated using specific quantitative real-time polymerase chain reaction. Its cellular function was then analyzed using immunofluorescent staining and the changes in the cell cycle in response to 5-fluorouracil (5-FU) were assessed.

Results: Gastrointestinal tissues and peripheral blood lymphocytes ubiquitously expressed KIAA0247. 56 CRC patients fell into two group categories according to fecal KIAA0247 mRNA expression levels. The group with higher fecal KIAA0247 (n=22; ≥0.4897) had a significantly greater five-year overall survival rate than the group with lower fecal KIAA0247 (n = 30; <0.4897) (66.0 ± 11.6%; p=0.035, log-rank test). Fecal expression of KIAA0247 inversely related to CRC tumor size (Kendall's tau-b=-0.202; p=0.047). Immunofluorescent staining revealed that the cytoplasm of CRC cells evenly expresses KIAA0247 without 5-FU treatment, and KIAA0247 accumulates in the nucleus after 40 μM 5-FU treatment. In HCT116 p53(-/-) cells, which lack p53 cell cycle control, the proportion of cells in the G2/M phase was larger (13%) in KIAA0247-silent cells than in the respective shLuc control (10%) and KIAA0247-overexpressing cells (7%) after the addition of low dose (40 μM) 5-FU. Expression of three cyclin genes (cyclin A2, cyclin B1, and cyclin B2) also downregulated in the cells overexpressing KIAA0247.

Conclusions: This is the first description of a linkage between KIAA0247 and CRC. The study's data demonstrate overexpression of KIAA0247 associates with 5-FU therapeutic benefits, and also identify the clinical significance of fecal KIAA0247 in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Cycle / drug effects*
  • Cell Division / drug effects
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Complement System Proteins / genetics
  • Complement System Proteins / metabolism*
  • Cyclins / genetics
  • Cyclins / metabolism
  • Feces
  • Female
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use*
  • G2 Phase / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Male
  • Membrane Proteins
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis

Substances

  • Cyclins
  • Membrane Proteins
  • RNA, Messenger
  • SUSD6 protein, human
  • Complement System Proteins
  • Fluorouracil