Stress-Induced Differential miR-4633-5p Expression in Thyroid Cancer Health Disparities

Abstract

Filipino Americans (FA) are known to have higher rates of thyroid cancer incidence and disease recurrence compared to European Americans (EA). FA are also known to be two times more likely to die of thyroid cancer compared to EA. Epidemiological studies in California have shown that thyroid cancer is the second most common cancer among FA women. Currently, there are no studies that demonstrate the mechanism behind these discrepancies. Evidence shows a strong correlation between obesity and more aggressive forms of thyroid cancer; obesity has an increased frequency in FA populations. The exact connection between the mechanisms of obesity and cancer is poorly understood. This epigenetic phenomenon may be due to microRNAs (miRNAs), which post-transcriptionally regulate gene expression. Dysregulated miRNA profiles have been associated with various diseases including obesity and cancer. MiRNAs are linked to different types of cancer; tumor suppressor genes and oncogenes are subject to modulation by dysregulated miRNAs. No study elucidates the association of miRNAs to tumor staging or prognosis in thyroid cancer health disparities. In this study, we determined miRNA expression profiles and found significant differences in the miRNA profiles between FA and EA thyroid cancer patients. Our pilot study showed several dysregulated miRNAs, from which we chose to assay dysregulated miR-4633-5p segments that are known to be associated with thyroid cancer signaling. We used QIAGEN’s miRNA extraction kit to obtain high-quality miRNA from paraffin-embedded thyroid tissues. We performed next-generation miRNA sequencing using equal number of FA and EA samples and identified the top ten significantly up- and down-regulated miRNAs from the pool of differentially expressed miRNAs by qPCR assays. Our investigation demonstrated a 1.5-2-fold higher expression of an upregulated miR-4633-5p in FA versus EA miRNA samples (n=70) after normalized to controls. In contrast, miR-323b-3p showed no difference between FA and EA after normalized to controls. For our future work, we plan to analyze multiple up- and down-regulated miRNAs by qPCR, determine whether the miRNA signatures are consistent between samples from FA versus EA, and explore the use of these miRNA signature differentials for affordable and rapid thyroid cancer screening and prognosis.