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Tumor Biology

, Volume 37, Issue 3, pp 4183–4192 | Cite as

The role of miR-145 in stem cell characteristics of human laryngeal squamous cell carcinoma Hep-2 cells

  • Omer Faruk Karatas
  • Ilknur Suer
  • Betul Yuceturk
  • Mehmet Yilmaz
  • Yusif Hajiyev
  • Chad J. Creighton
  • Michael Ittmann
  • Mustafa Ozen
Original Article

Abstract

The cancer stem-like cells (CSLCs) are tumorigenic cells promoting initiation, progression, and spread of the tumor. Accumulating evidences suggested the presence of CSLCs in distinct tumors including laryngeal squamous cell carcinoma (LSCC). MicroRNAs have been proposed as significant regulators of carcinogenesis, and several of them have been demonstrated to have direct roles in survival of CSLCs. In this study, we aimed to explore the role of miR-145, which is downregulated in LSCC, on cancer stem cell potency of laryngeal cancer cells. We initially showed the downregulation of miR-145 expression in tumor tissue samples and in CD133-enriched CSLCs. Quantitative reverse-transcription PCR (qRT-PCR) analysis of miR-145-transfected Hep-2 cells demonstrated the inhibitory role of miR-145 on stem cell markers like SOX2, OCT4, KLF4, and ABCG2. We, then, investigated the stem cell features of miR-145-overexpressing Hep-2 cells by sphere formation assay, single-cell cloning assay, and aldehyde dehydrogenase (ALDH) assay, which all demonstrated the inhibition of stem cell potency upon miR-145 overexpression. Further qRT-PCR analysis demonstrated altered expression of epithelial to mesenchymal transition markers in miR-145-overexpressing Hep-2 cells. In conclusion, we demonstrated the regulatory role of miR-145 in stem cell characteristics of Hep-2 cells. Based on these results, we propose that miR-145 might carry crucial roles in LSCC tumorigenesis, prognosis, metastasis, chemoresistance, and recurrence through regulating stem cell properties of tumor cells.

Keywords

Hsa-miR-145 Laryngeal squamous cell carcinoma Stem cell markers Cancer stem-like cells 

Notes

Acknowledgments

We thank Yiqun Zhang for technical assistance in microarray analysis. The studies presented in this manuscript were partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK, grant number 210T009) and by the US National Cancer Institute grant P30CA125123.

Compliance with ethical standards

This study has been reviewed and approved by an institutional review board of Istanbul University, Cerrahpasa Medical School (IRB No. 35697).

Conflicts of interest

None

Informed consent

Patients were included into the study after each of them signed written informed consent forms.

Supplementary material

13277_2015_4219_MOESM1_ESM.xlsx (72 kb)
ESM 1 (XLSX 72 kb)
13277_2015_4219_Fig6_ESM.jpg (45 kb)
Supplementary Figure 1

(JPEG 44 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Omer Faruk Karatas
    • 1
  • Ilknur Suer
    • 2
  • Betul Yuceturk
    • 2
    • 3
  • Mehmet Yilmaz
    • 4
  • Yusif Hajiyev
    • 5
  • Chad J. Creighton
    • 6
  • Michael Ittmann
    • 7
    • 8
  • Mustafa Ozen
    • 2
    • 7
    • 9
  1. 1.Molecular Biology and Genetics DepartmentErzurum Technical UniversityErzurumTurkey
  2. 2.Department of Medical Genetics, Cerrahpasa Medical SchoolIstanbul UniversityIstanbulTurkey
  3. 3.Advanced Genomics and Bioinformatics Research CenterThe Scientific and Technological Research Council of Turkey (TUBITAK)GebzeTurkey
  4. 4.Department of Otorhinolaryngology, Cerrahpasa Medical SchoolIstanbul UniversityIstanbulTurkey
  5. 5.Department of OtorhinolaryngologyAzerbaijan Medical UniversityBakuAzerbaijan
  6. 6.Department of Medicine and Dan L. Duncan Cancer Center Division of BiostatisticsBaylor College of MedicineHoustonUSA
  7. 7.Department of Pathology and ImmunologyBaylor College of MedicineHoustonUSA
  8. 8.Michael E. DeBakey VAMCHoustonUSA
  9. 9.Department of Medical Genetics/Molecular Biology and GeneticsBiruni UniversityTopkapiTurkey

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