Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma

Arunkumar,Ganesan; Deva Magendhra Rao,Arunagiri   Kuha; Manikandan,Mayakannan; Prasanna Srinivasa Rao,Harikrishnan; Subbiah,Shanmugam; Ilangovan,Ramachandran; Murugan,Avaniyapuram   Kannan; Munirajan,Arasambattu  Kannan

doi:10.3892/ol.2017.7296

Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma

Authors:
- Ganesan Arunkumar
- Arunagiri Kuha Deva Magendhra Rao
- Mayakannan Manikandan
- Harikrishnan Prasanna Srinivasa Rao
- Shanmugam Subbiah
- Ramachandran Ilangovan
- Avaniyapuram Kannan Murugan
- Arasambattu Kannan Munirajan
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Affiliations: Department of Genetics, Dr. A.L.M. PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India, Center for Oncology, Royapettah Government Hospital and Kilpauk Medical College, Royapettah, Chennai 600014, India, Department of Endocrinology, Dr. A.L.M. PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
Published online on: October 31, 2017 https://doi.org/10.3892/ol.2017.7296
Pages: 649-657

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Abstract

MicroRNAs (miRNAs) are reported to function as a major component in the cellular signaling circuit, which regulates epithelial‑mesenchymal transition (EMT). Dysregulation of the microRNA‑200 (miR‑200) family and EMT‑associated genes enables tumor metastasis and resistance to therapy. The present study profiled miR‑200 family members miR‑200a, miR‑200b, miR‑200c, miR‑141 and miR‑429, and also several EMT‑regulatory genes including zinc finger E‑box‑binding homeobox (ZEB)1, ZEB2, epithelial cadherin and vimentin in 40 oral primary tumors in order to understand their role(s) in oral squamous cell carcinoma (OSCC). The reverse transcription‑quantitative polymerase chain reaction was used to analyze each sample. Results demonstrated a significant downregulation of miR‑200 family members in tumors with a history of tobacco chewing/smoking (P<0.0006, P=0.0467, P=0.0014, P=0.0087 and P=0.0230, respectively) and undifferentiated pathology (miR‑200a, P=0.0067; miR‑200c, P=0.0248). EMT markers ZEB2 (P=0.0451) and vimentin (P=0.0071) were significantly upregulated in the oral tumors. Furthermore, ZEB2 antisense RNA1 was overexpressed in 50% of OSCC samples (P=0.0075). EMT‑regulatory genes did not exhibit any association with clinical outcome. The present study also analyzed the expression of EMT‑regulatory genes in 523 head and neck squamous cell carcinoma (HNSCC) samples from The Cancer Genome Atlas (TCGA) database, and the association with treatment outcome. Analysis of TCGA datasets also demonstrated no significant association in the expression of EMT markers with disease recurrence and treatment outcome. The results of the present study revealed dysregulation of miR‑200 family miRNAs and EMT‑regulatory genes in OSCC without any significant effect on treatment outcome.

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