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The Keap1/Nrf2 Signaling Pathway in the Thyroid-2020 Update.

ABSTRACT: The thyroid gland has a special relationship with oxidative stress. On the one hand, like all other tissues, it must defend itself against reactive oxygen species (ROS). On the other hand, unlike most other tissues, it must also produce reactive oxygen species in order to synthesize its hormones that contribute to the homeostasis of other tissues. The thyroid must therefore also rely on antioxidant defense systems to maintain its own homeostasis in the face of continuous self-exposure to ROS. One of the main endogenous antioxidant systems is the pathway centered on the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1). Over the last few years, multiple links have emerged between the Keap1/Nrf2 pathway and thyroid physiology, as well as various thyroid pathologies, including autoimmunity, goiter, hypothyroidism, hyperthyroidism, and cancer. In the present mini-review, we summarize recent studies shedding new light into the roles of Keap1/Nrf2 signaling in the thyroid.

SUBMITTER: Thanas C

PROVIDER: S-EPMC7693470 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The Keap1/Nrf2 Signaling Pathway in the Thyroid-2020 Update.

Thanas Christina C Ziros Panos G PG Chartoumpekis Dionysios V DV Renaud Cédric O CO Sykiotis Gerasimos P GP

Antioxidants (Basel, Switzerland) 20201104 11

The thyroid gland has a special relationship with oxidative stress. On the one hand, like all other tissues, it must defend itself against reactive oxygen species (ROS). On the other hand, unlike most other tissues, it must also produce reactive oxygen species in order to synthesize its hormones that contribute to the homeostasis of other tissues. The thyroid must therefore also rely on antioxidant defense systems to maintain its own homeostasis in the face of continuous self-exposure to ROS. On ...[more]

PMID: 33158045

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Project description:BackgroundNucleolar protein 16 (NOP16) is present in the protein complex of the nucleolus. The NOP16 promoter contains a c-Myc binding site, and the transcriptional regulation by c-Myc directly regulates NOP16 expression levels.ObjectiveDysregulation of NOP 16 is currently reported in only a small number of cancers. In this study, the expression profile of NOP 16 in hepatocellular carcinoma (LIHC) and its clinical significance were analyzed.MethodsNOP16 expression in hepatocellular carcinoma (LIHC) and its relationship with the clinical characters of LIHC were examined using the Cancer Genome Atlas (TCGA), the Gene Expression comprehensive database (GEO), Kaplan-Meier survival analysis, univariate Cox analysis, multivariate Cox analysis, ROC curve analysis of KEGG enrichment, GSEA enrichment, in vitro experiments (e.g., siRNA interference of NOP16 expression in hepatoma cells, Keap1-Nrf2 pathway, cell cycle, cell apoptosis and Transwell assays), and LIHC single-cell sequencing (scRNA).ResultsPan-cancer analysis revealed that NOP16 was highly expressed in 20 cancer types, including LIHC, and high NOP16 expression was an independent adverse prognostic factor in LIHC patients. The expression levels of NOP16 mRNA and protein were significantly increased in tumour tissues of LIHC patients compared to normal tissues. The functions of co-expressed genes were primarily enriched in the cell cycle and reactive oxygen species metabolism. The experimental results showed that knockdown of NOP16 activated the Keap/Nrf2 signalling pathway and inhibited the invasion, migration, and EMT progression of LIHC cells. LIHC scRNA-seq data showed that NOP16 was primarily expressed in T lymphocytes.ConclusionsNOP16 promoted cancer development in LIHC and caused an imbalance in Keap/Nrf2 signalling, which subsequently caused the aberrant expression of genes typical for EMT, cell cycle progression and apoptosis. NOP16 is a potential prognostic marker and therapeutic target for hepatocellular carcinoma progression.

Dataset Information

The Keap1/Nrf2 Signaling Pathway in the Thyroid-2020 Update.

Publications

The Keap1/Nrf2 Signaling Pathway in the Thyroid-2020 Update.

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