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IFITM3 knockdown reduces the expression of CCND1 and CDK4 and suppresses the growth of oral squamous cell carcinoma cells

  • Chai Phei Gan
  • Kin Kit Sam
  • Pei San Yee
  • Nur Syafinaz Zainal
  • Bernard Kok Bang Lee
  • Zainal Ariff Abdul Rahman
  • Vyomesh Patel
  • Aik Choon Tan
  • Rosnah Binti Zain
  • Sok Ching CheongEmail author
Original Paper
  • 59 Downloads

Abstract

Purpose

Oral squamous cell carcinoma (OSCC) is a challenging disease to treat. Up to 50% of OSCC patients with advanced disease develop recurrences. Elucidation of key molecular mechanisms underlying OSCC development may provide opportunities to target specific genes and, thus, to improve patient survival. In this study, we examined the expression and functional role of interferon transmembrane protein 3 (IFITM3) in OSCC development.

Methods

The expression of IFITM3 in OSCC and normal oral mucosal tissues was assessed by qRT-PCR and immunohistochemistry. The role of IFITM3 in driving OSCC cell proliferation and survival was examined using siRNA-mediated gene knockdown, and the role of IFITM3 in driving cell cycle regulators was examined using Western blotting.

Results

We found that IFITM3 is overexpressed in more than 79% of primary OSCCs. We also found that IFITM3 knockdown led to impaired OSCC cell growth through inhibition of cell proliferation, induction of cell cycle arrest, senescence and apoptosis. In addition, we found that IFITM3 knockdown led to reduced expressions of CCND1 and CDK4 and reduced RB phosphorylation, leading to inhibition of OSCC cell growth. This information may be instrumental for the design of novel targeted therapeutic strategies.

Conclusions

From our data we conclude that IFITM3 is overexpressed in OSCC and may regulate the CCND1-CDK4/6-pRB axis to mediate OSCC cell growth.

Keywords

Oral squamous cell carcinoma IFITM3 Proliferation CCND1 CDK4 

Notes

Acknowledgments

We would like to thank all consented patients who participated in this study. This study was funded by Ministry of Science, Technology and Innovation (MOSTI 06-00-00-0000), University of Malaya (UM.C/625/1/HIR/MOHE/DENT-03) and sponsors of Cancer Research Malaysia. Cancer Research Malaysia is a non-profit research organization. We are committed to an understanding of cancer prevention, diagnosis and treatment through a fundamental research program.

Compliance with ethical standards

Conflict of interest

All authors declared that they have no conflict of interest.

Supplementary material

13402_2019_437_Fig6_ESM.png (2.5 mb)
Supplementary fig. 1

mRNA expression of IFITM family members in head and neck cancer in TCGA database (PNG 2550 kb)

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High Resolution Image (TIF 654 kb)
13402_2019_437_Fig7_ESM.png (530 kb)
Supplementary fig. 2

(a) Endogenous expression of IFITM3 in oral cancer cell lines. (b&c) Specific IFITM3 knockdown by si18 determined by qRT-PCR analysis (PNG 529 kb)

13402_2019_437_MOESM2_ESM.tif (1014 kb)
High Resolution Image (TIF 1014 kb)
13402_2019_437_Fig8_ESM.png (1.5 mb)
Supplementary fig. 3

Microscopic view of cells after transfection with si18. Morphological changes and floating cells are apparent after IFITM3 knockdown compared to that in NT siRNA cells. (b) Microscopic view of soft agar assay comparing IFITM3 knockdown cells with NT siRNA cells (PNG 1537 kb)

13402_2019_437_MOESM3_ESM.tif (2.3 mb)
High Resolution Image (TIF 2343 kb)
13402_2019_437_MOESM4_ESM.docx (18 kb)
Supplementary Table 1 (DOCX 18 kb)

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Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  • Chai Phei Gan
    • 1
  • Kin Kit Sam
    • 1
  • Pei San Yee
    • 1
  • Nur Syafinaz Zainal
    • 1
  • Bernard Kok Bang Lee
    • 1
  • Zainal Ariff Abdul Rahman
    • 2
  • Vyomesh Patel
    • 1
  • Aik Choon Tan
    • 3
  • Rosnah Binti Zain
    • 4
  • Sok Ching Cheong
    • 1
    • 2
    Email author
  1. 1.Head and Neck Cancer Research TeamCancer Research MalaysiaSubang JayaMalaysia
  2. 2.Department of Oral & Maxillofacial Clinical Sciences, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia
  3. 3.Division of Medical Oncology, School of MedicineUniversity of Colorado Anschutz Medical CampusAuroraUSA
  4. 4.Oral Cancer Research & Coordinating Centre (OCRCC), Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia

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