Knockdown of copper chaperone antioxidant-1 by RNA interference inhibits copper-stimulated proliferation of non-small cell lung carcinoma cells

Huawei Cai, Fangyu Peng

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Copper is required for cell proliferation and tumor angiogenesis. Cellular copper metabolism is regulated by a network of copper transporters and chaperones. Antioxidant-1 (ATOX1) is a cytosolic copper chaperone important for intracellular copper transport, which plays a role in the regulation of cell proliferation by functioning as a transcription factor in cell growth signal-transduction pathways. The present study aimed to explore the role of ATOX1 in the copper-related regulation of lung cancer cell proliferation by immunohistochemical (IHC) analysis of ATOX1 expression in non-small cell lung cancer (NSCLC) tissue samples and by assessing the effects of RNA interference (RNAi)-mediated knockdown of ATOX1 on copper-stimulated proliferation of NSCLC cells. Overexpression of ATOX1 was detected in NSCLC by IHC analysis of the tissue samples from patients diagnosed with NSCLC when compared with expression of ATOX1 in non-malignant lung tissue samples. Knockdown of ATOX1 in the NSCLC cells transduced by a lentiviral vector encoding short hairpin RNA (shRNA) specific for ATOX1 was associated with reduction in copper-stimulated cell proliferation. These findings suggest that ATOX1 plays an important role in copper-stimulated proliferation of NSCLC cells and ATOX1 holds potential as a therapeutic target for lung cancer therapy targeting copper metabolism.

Original languageEnglish (US)
Pages (from-to)269-275
Number of pages7
JournalOncology Reports
Volume30
Issue number1
DOIs
StatePublished - Jul 2013

Fingerprint

RNA Interference
Non-Small Cell Lung Carcinoma
Copper
Antioxidants
Cell Proliferation
Lung Neoplasms
Small Interfering RNA
Signal Transduction
Transcription Factors
Lung
Therapeutics
Growth

Keywords

  • Antioxidant-1
  • Cancer therapy
  • Copper chaperones
  • Copper metabolism
  • Non-small cell lung carcinoma
  • RNA interference

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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abstract = "Copper is required for cell proliferation and tumor angiogenesis. Cellular copper metabolism is regulated by a network of copper transporters and chaperones. Antioxidant-1 (ATOX1) is a cytosolic copper chaperone important for intracellular copper transport, which plays a role in the regulation of cell proliferation by functioning as a transcription factor in cell growth signal-transduction pathways. The present study aimed to explore the role of ATOX1 in the copper-related regulation of lung cancer cell proliferation by immunohistochemical (IHC) analysis of ATOX1 expression in non-small cell lung cancer (NSCLC) tissue samples and by assessing the effects of RNA interference (RNAi)-mediated knockdown of ATOX1 on copper-stimulated proliferation of NSCLC cells. Overexpression of ATOX1 was detected in NSCLC by IHC analysis of the tissue samples from patients diagnosed with NSCLC when compared with expression of ATOX1 in non-malignant lung tissue samples. Knockdown of ATOX1 in the NSCLC cells transduced by a lentiviral vector encoding short hairpin RNA (shRNA) specific for ATOX1 was associated with reduction in copper-stimulated cell proliferation. These findings suggest that ATOX1 plays an important role in copper-stimulated proliferation of NSCLC cells and ATOX1 holds potential as a therapeutic target for lung cancer therapy targeting copper metabolism.",
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