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Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer

Endocrinology and Metabolism 2020년 35권 3호 p.656 ~ 668
정선향, 김인규, 김현지, 최문정, 이잔디, 조영석,
소속 상세정보
정선향 ( Jeong Seon-Hyang ) - Yonsei University College of Medicine Department of Internal Medicine
김인규 ( Kim In-Kyu ) - Yonsei University College of Medicine Severance Hospital Department of Surgery
김현지 ( Kim Hyun-Ji ) - Yonsei University College of Medicine Severance Hospital Department of Surgery
최문정 ( Choi Moon-Jung ) - Yonsei University College of Medicine Severance Hospital Department of Surgery
이잔디 ( Lee Jan-Dee ) - Yonsei University College of Medicine Severance Hospital Department of Surgery
조영석 ( Jo Young-Suk ) - Yonsei University College of Medicine Department of Internal Medicine

Abstract


Background: Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features.

Methods: Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort.

Results: In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets.

Conclusion: The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

키워드

Thyroid neoplasms; Obesity; Metabolism; Prognosis; Liver X receptors; Ribosomes

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