Structural maintenance of chromosomes 4 is a predictor of survival and a novel therapeutic target in colorectal cancer

Asian Pac J Cancer Prev. 2014;15(21):9459-65. doi: 10.7314/apjcp.2014.15.21.9459.

Abstract

Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood.

Materials and methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis.

Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree.

Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomes, Human*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging / methods
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • RNA, Messenger
  • Adenosine Triphosphatases
  • SMC4 protein, human