CD44 silencing decreases the expression of stem cell-related factors induced by transforming growth factor β1 and tumor necrosis factor α in lung cancer: Preliminary findings

  • Fariz Nurwidya Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Pulmonology and Respiratory Medicine, Universitas Indonesia Faculty of Medicine, Jakarta, Indonesia http://orcid.org/0000-0002-8379-9510
  • Fumiyuki Takahashi Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Motoyasu Kato Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Hario Baskoro Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Moulid Hidayat Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Aditya Wirawan Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Kazuhisa Takahashi Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
Keywords: CD44, CXCR4 receptor, Oct4, POU5F1, non-small cell lung cancer cells, NSCLC, C-X-C chemokine receptor type 4, octamer-binding transcription factor 4

Abstract

The mechanism underlying increased concentrations of cancer stem cell (CSC)-associated factors in non-small cell lung cancer (NSCLC) cells treated with transforming growth factor β1 (TGFβ1) and tumor necrosis factor α (TNFα), is still not clear. The purpose of this study was to investigate the possible role of CD44 in the regulation of CSC-associated genes, by analyzing the effect of CD44 knockdown on their expression. A549, a NSCLC cell line that expresses CD44 antigen, was treated with TGFβ1 and TNFα. Small-interfering ribonucleic acid (siRNA) that specifically targets the CD44 gene was used to knockdown the expression of CD44 in A549. The gene expressions of CD44, CXCR4, POU5F1 (octamer-binding transcription factor 4 [Oct4]), PROM1, NANOG, c-Myc, KLF4, and SOX2, as well as of CDH1 (E-cadherin), CDH2 (N-cadherin), VIM (vimentin), and FN1 (fibronectin) were analyzed in A549 cells by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell morphology was observed using light microscopy. After TGFβ1/TNFα treatment, increased expressions of CXCR4 and POU5F1 were detected. Silencing of CD44 gene expression was confirmed by RT-qPCR. The knockdown of CD44 decreased the CXCR4 and POU5F1 gene expressions in TGFβ1/TNFα-treated A549 cells. However, the silencing of CD44 did not affect the morphology of TGFβ1/TNFα-treated A549 cells nor it reversed epithelial-mesenchymal transition (EMT) gene signature induced by TGFβ1/TNFα in A549 cells. Our preliminary findings suggest that the CD44 gene may have a role in regulating CXCR4 and POU5F1 gene expressions, independently of the EMT signaling pathway.

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Author Biographies

Fariz Nurwidya, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Pulmonology and Respiratory Medicine, Universitas Indonesia Faculty of Medicine, Jakarta, Indonesia

Department of Respiratory Medicine

Department of Pulmonology and Respiratory Medicine

Fumiyuki Takahashi, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan

Department of Respiratory Medicine

Motoyasu Kato, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
Department of Respiratory Medicine
Hario Baskoro, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
Department of Respiratory Medicine
Moulid Hidayat, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
Department of Respiratory Medicine
Aditya Wirawan, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
Department of Respiratory Medicine
Kazuhisa Takahashi, Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Graduate School of Medicine, Tokyo, Japan
Department of Respiratory Medicine

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Published
2017-08-20
How to Cite
1.
Nurwidya F, Takahashi F, Kato M, Baskoro H, Hidayat M, Wirawan A, Takahashi K. CD44 silencing decreases the expression of stem cell-related factors induced by transforming growth factor β1 and tumor necrosis factor α in lung cancer: Preliminary findings. Bosn J of Basic Med Sci [Internet]. 2017Aug.20 [cited 2019Nov.13];17(3):228-34. Available from: http://bjbms.org/ojs/index.php/bjbms/article/view/1966
Section
Molecular Biology