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. 2015 May;7(5):145-154.
doi: 10.4172/1948-5956.1000340.

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

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Free PMC article

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

Raagini Suresh et al. J Cancer Sci Ther. .
Free PMC article

Abstract

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 qRT-PCR, 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.

Keywords: FFPE; Papillary thyroid cancer; Racial disparity; Targeted therapies; miRNAs; qRT-PCR.

Conflict of interest statement

Conflict of Interest

All the authors declare no competing conflict of interest.

Figures

Figure 1
Figure 1
A hierarchical clustering and heat maps of the miRNA profiling of Caucasian American (normal vs tumor samples), up-regulated in tumor samples (A) and down-regulated in tumor samples (B).
Figure 2
Figure 2
Ingenuity pathway analysis showing up (green) and down-regulation (red) of miRNAs involved in papillary thyroid cancer (PTC) tumor samples when compared to normal samples. Target genes are also represented, such as RAS, NF-κB, VEGF, and P38 MAPK pathways.
Figure 3
Figure 3
Comparative expression analysis of miR-21 and miR-146b in 18 paired samples of FFPE cell blocks of tumor and normal tissue from papillary thyroid carcinoma (PTC) patients’ individually using qRT-PCR. Combined data for both races (A and C) and race-specific data (B and D) is presented. There was a significant up-regulation of miRNA-21 in African American (AA) patients when compared to Caucasian American (CA) patients (3B). Overall, while miR-146b appears to be up-regulated, a larger percentage of CA samples than AA samples followed this trend (3D). The miRNAs expression was normalized using RNU48 miRNA. P values represent comparison between normal and tumor (3A, 3C), and CA tumor vs AA tumor (3B, 3D) using F test.
Figure 4
Figure 4
Comparative expression analysis of miR-221 and miR-222 in 18 paired samples of FFPE cell blocks of tumor and normal tissue from PTC patients’ individually using qRT-PCR. Combined data for both races (A and C) and race-specific data (B and D) is presented. For miR-221, there appears to be greater up-regulation in CA tumors than in AA tumors (4B). No such race-specific difference was observed for miR-222. The miRNAs expression was normalized using RNU48 miRNA. P values represent comparison between normal and tumor (4A, 4C), and CA tumor vs AA tumor (4B, 4D) using F test.
Figure 5
Figure 5
Comparative expression analysis of miR-31 and miR-3613 in 22 paired samples of FFPE cell blocks of tumor and normal tissue in PTC patients’ individually using qRT-PCR. Combined data for both races (A and C) and race-specific data (B and D) is presented. In combined data for miR-31, there appears to be no trend regarding differential miRNA expression (5A). When individual races were examined, miR-31 was mostly up-regulated in CA patients and primarily down-regulated in AA patients (5B). No such race-specific difference was observed in miR-3613. The miRNAs expression was normalized using RNU48 miRNA. P values represent comparison between normal and tumor (5A, 5C), and CA tumor vs AA tumor (5B, 5C) using F test.
Figure 6
Figure 6
Comparative expression analysis of miR-138 in 18 paired samples and miR-98 in 22 paired samples of FFPE cell blocks of tumor and normal tissue from PTC patients’ individually using qRT-PCR. Combined data for both races (A and C) and race-specific data (B and D) is presented. No clear trend was present for miR-98 expression in CA. However, in AA, 80% of tumors had down-regulated miR-138 (Figure 6B). The miRNAs expression was normalized using RNU48 miRNA. P values represent comparison between normal and tumor (6A, 6C), and CA tumor vs AA tumor (6B, 6D) using F test.

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