Identification of Oncosuppressing Effects of Seven Selenoproteins in Thyroid Cancer: Implications for Distinct Roles of Selenoproteins in Tumorigenesis

Abstract

Background: Low selenium levels are associated with increased incidence and advanced stage of thyroid cancers. In response to changes in selenium levels, a hierarchy of selenoprotein biosynthesis allows tissue-specific fine-tuning of the 25 selenoproteins. To determine the role of individual selenoproteins on thyroid carcinogenesis, we carried out a multiomic data mining study.Methods: The expressions of individual selenoproteins and their correlation with prognosis in thyroid cancers were analyzed using Oncomine, GEPIA and Kaplan–Meier plotter platforms. Co-expression analysis using cBioportal database was carried out to identify genes that are correlated with selenoproteins. GO and KEGG enrichment were further performed for genes correlated with selenoproteins that are clinically significant.Results: DIO1, GPX3, SELENOP, SELENOM SELENOS, SELENOO and SELENOV were significantly downregulated and with a poor prognosis in thyroid cancers. 35 biological processes including GO: 0045926 (negative regulation of growth) and 23 biological processes including GO:0001525 (angiogenesis) and GO:0007155 (cell adhesion) were enriched in DIO1-positively and DIO1-negatively correlated genes, respectively. 41 biological processes including GO: 0045926 (negative regulation of growth) and 23 biological processes including GO:0007165 (signal transduction) and GO: 0000165 (MAPK cascade) were enriched in GPX3-positively and GPX3-negatively correlated genes, respectively. The antitumor effects of SELENOM and SELENOS might be attributed to their protection against endoplasmic reticulum (ER) stress. SELENOO was revealed to be correlated with ER stress, mitochondria translation and telomere maintenance. Biological processes of SELENOV-correlated genes were enriched in oxidation-reduction process and ER calcium ion homeostasis. Moreover, cell adhesion and angiogenesis were also shown to be negatively regulated by SELENOV, providing an anti-metastatic effect similar as DIO1.Conclusion: This study confirms the distinct roles of the 25 selenoproteins in thyroid cancer pathogenesis, providing useful information to uncover the currently unknown functions of selenoproteins and open up the possibility for targeted regulation of individual selenoproteins for treatment of thyroid cancer.