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Published on: June 15, 2016
Delineating the regulatory axis of miR-20a, STAT3, and IL-6 in oral squamous cell carcinoma
Priya Thomas1, Abilasha Ramasubramanian2, Durairaj Sekar3
1Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Science (SIMATS); Department of Oral Pathology & Microbiology, Annoor Dental College & Hospital, Muvattupuzha, Kerala, India.
Aim:
To investigate the regulatory role of miR-20a and its basal levels in the STAT3/IL-6 pathway in OSCC tissues, and assessing the concomitant role of miR-20a and STAT3, particularly the miR-20a's inhibitory role on STAT3 in OSCC progression.
Materials & Methods:
Biopsied specimens were obtained from 63 OSCC individuals. RNA isolation was performed using TRIzol, and cDNA was generated for quantitative real-time PCR to analyze miR-20a, STAT3, and IL-6 levels across paired OSCC and adjacent noncancerous tissues. The protein expression of STAT3 and IL-6 were evaluated using western blot in both normal and OSCC samples. Data were transferred to Microsoft Excel, and statistical analyses, including t-tests and ANOVA (p < 0.05), were conducted using GraphPad Prism. Clinicopathological correlation between miR-20a, STAT3, and IL-6 expression with tumor grade and histological staging were also explored.
Results:
In OSCC tissues, STAT3 and IL-6 mRNA and protein expressions were significantly higher, while miR-20a mRNA expression was significantly lower compared to corresponding nontumorous tissue. Analysis revealed that OSCC tissue samples exhibited marked difference in the levels of miR-20a, STAT3, and IL-6 expression, with very high statistical significance (p < 0.0001). An inverse relationship was noted: as miR-20a levels decreased with increasing tumor grade and clinical stage, STAT3 and IL-6 expressions varied.
Conclusion:
This study shows significant upregulation of STAT3 and IL-6 and downregulation of miR-20a in OSCC tissues samples suggesting miR-20a's potential as a tumor suppressor.
Clinical Significance:
miR-20a expression inversely correlates with STAT3 and IL-6 levels, declining with tumor progression and playing a key part in regulating the STAT3/IL-6 pathway. The observed characteristics of miR-20a indicate its potential application in OSCC diagnostics and targeted therapeutics. The antagonism between miR-20a and STAT3 emphasizes the value of miR-20a-based replacement and immunotherapy in personalized treatment strategies. Additionally, the expression profiles of miR-20a, STAT3, and IL-6 may function as potential indicators for early diagnosis and therapeutic intervention.
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