Estimation of Autophagy Activity By Evaluating Possible MicroRNA Biomarkers and FOXO1 mRNA Level in Papillary Thyroid Carcinoma

Abstract

Background: Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy. Despite nearly three-fold increase in incidence over three decades, the mortality rate remains unchanged. Biomarkers related to early diagnosis and prognosis of PTC are poorly investigated. Autophagy pathways and related miRNAs is considered to play an important role in PTC pathophysiology.Methods and Results: Tissue samples from patients with PTC undergoing thyroidectomy were collected. Total RNA content of tumor and margin samples were purified and converted to cDNA. Gene expression levels of mRNA (FOXO1) and miRNAs (miR-30d-5p, miR- 182-5p and miR-183-5p) were evaluated using qPCR method in PTC and adjacent normal tissue. A 6.51-fold decrease in miR-30d-5p level was detected in tumor samples compared to adjacent tissues. Moreover, miR-182-5p and miR-183-5p (FOXO1 as the main target) showed 1.73- and 4.31-fold increases in their levels, respectively. We also observed a 2.66-fold decrease in FOXO1 mRNA level in relation to these miRNA fold changes indicating a possible correlation between autophagy-linked molecular events and PTC.Conclusions: Significant increase in miR-183-5p and miR-182-5p expression, as well as a decrease in FOXO1 and miR-30d-5p expression, suggest that PTC has active autophagy machinery. This can possibly be used as a novel diagnostic or prognostic biomarker.

Phenotypic Transitions the Processes Involved in Regulation of Growth and Proangiogenic Properties of Stem Cells, Cancer Stem Cells and Circulating Tumor Cells

“…Mesenchymal properties and mobility of lung adenocarcinoma cells were repressed following CCL7 knockdown representing TAMs as EMT inducers [ 83 ]. Autophagy, a catabolic machinery essential for preservation of cellular homeostasis, also is a double-edge sword in tumor progression and is known to be dysregulated in many carcinomas [ 84 ]. There are crosslinks between EMT and autophagy pathways.…”