CUL4A expression in pediatric osteosarcoma tissues and its effect on cell growth in osteosarcoma cells

Tumour Biol. 2016 Jun;37(6):8139-44. doi: 10.1007/s13277-015-4715-1. Epub 2015 Dec 29.

Abstract

Osteosarcoma (OS) is the most common bone malignancy in the pediatric population, and it comprises about 3 % of all pediatric tumors. Aberrant expression of the Cullin 4A (CUL4A) is found in many tumor types, but the role of CUL4A in OS progression remains largely unknown. The aim of this study was to investigate the expression and function of CUL4A in OS. CUL4A expression was detected in 30 samples of surgically resected OS and matched tumor-adjacent tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Cell proliferation was assessed by MTT, and migration and invasion were analyzed by Transwell and Matrigel assays after CUL4A knockdown in OS in vitro. Our result showed increased CUL4A expression in OS tissues. CUL4A knockdown inhibited the proliferation of MG63 cells. Furthermore, CUL4A siRNA ameliorated the migration and invasion of MG63 cell lines with altered expression of epithelial-mesenchymal transition (EMT)-associated molecules. Taken together, our findings indicate that CUL4A plays a pivotal role in OS progression and may serve as a potential marker for clinical diagnosis and target for therapy.

Keywords: CUL4A; EMT; Invasion; Osteosarcoma; Proliferation; Targeted therapy.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cullin Proteins / antagonists & inhibitors
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism*
  • Epithelial-Mesenchymal Transition
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Infant
  • Infant, Newborn
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CUL4A protein, human
  • Cullin Proteins
  • RNA, Messenger
  • RNA, Small Interfering