Раковая наука и терапия

Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity

Abstract

Raagini Suresh, Seema Sethi, Shadan Ali, Tamar Giorgadze and Fazlul H. Sarkar

Objective: MicroRNAs (miRNAs) are known to play important roles in the diagnosis and prognosis of papillary thyroid cancer (PTC), and they are useful in developing targeted therapies. However, there have been no studies on the existence of racial differences in miRNAs expression that could explain differential overall survival of PTC patients. Expression analysis of miRNAs in major racial groups would be important for optimizing personalized treatment strategies. In the current study, we assessed the differential expression of 8 miRNAs between normal and tumor tissues, and also assessed racial differences between African American (AA) and Caucasian American (CA).

Methods: First, the miRNA expression profiling was performed using formalin-fixed paraffin embedded (FFPE) tissue sections of tumor containing over 70% tumor cells. Normal and tumor sections of thyroid tissues were studied from AA and CA patients. The miRNA microarray profiling was done using miRBase version 18 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was used to validate expression of 8 selected miRNAs.

Results: Ingenuity pathway analysis showed involvement of target genes, such as Ras and NF-κB. Deregulated miRNAs such as miR-221 and miR-31 were found to be statistically significant between the two races. Using qRTPCR, we found that miR-21, miR-146b, miR-221, miR-222, miR-31, and miR-3613 were up-regulated while miR- 138 and miR-98 were down-regulated in tumors compared to normal tissues.

Conclusion: Though sample size was small, we found several deregulated miRNAs having racial differences. The differential expression of miRNAs suggest that these miRNAs and their target genes could be useful to gain further mechanistic insight of PTC and their clinical implications, including miRNA replacement therapy or their knockdown strategies.