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HIF2α-induced upregulation of RNASET2 promotes triglyceride synthesis and enhances cell migration in clear cell renal cell carcinoma.
Quan, Yanmei; Dai, Jun; Zhou, Sian; Zhao, Lingyi; Jin, Lixing; Long, Yijing; Liu, Siwei; Hu, Yanqin; Liu, Yue; Zhao, Juping; Ding, Zhide.
Afiliación
  • Quan Y; Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Dai J; Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
  • Zhou S; Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Zhao L; Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Jin L; Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Long Y; Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Liu S; Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Hu Y; Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Liu Y; Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China.
  • Zhao J; Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
  • Ding Z; Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China.
FEBS Open Bio ; 13(4): 638-654, 2023 04.
Article en En | MEDLINE | ID: mdl-36728187
Clear cell renal cell carcinoma (ccRCC), the most common malignant subtype of renal cell carcinoma, is characterized by the accumulation of lipid droplets in the cytoplasm. RNASET2 is a protein coding gene with a low expression level in ovarian cancers, but it is overexpressed in poorly differentiated neuroendocrine carcinomas. There is a correlation between RNASET2 upregulation and triglyceride expression levels in human serum but is unknown whether such an association is a factor contributing to lipid accumulation in ccRCC. Herein, we show that RNASET2 expression levels in ccRCC tissues and cell lines are significantly higher than those in both normal adjacent tissues and renal tubular epithelial cells. Furthermore, its upregulation is associated with increases in ccRCC malignancy and declines in patient survival. We also show that an association exists between increases in both cytoplasmic lipid accumulation and HIF-2α transcription factor upregulation, and increases in both RNASET2 and triglyceride expression levels in ccRCC tissues. In addition, DGAT1 and DGAT2, two key enzymes involved in triglyceride synthesis, are highly expressed in ccRCC tissues. By contrast, RNASET2 knockdown inhibited their expression levels and lowered lipid droplet accumulation, as well as suppressing in vitro cell proliferation, cell invasion, and migration. In conclusion, our data suggest HIF2α upregulates RNASET2 transcription in ccRCC cells, which promotes both the synthesis of triglycerides and ccRCC migration. As such, RNASET2 may have the potential as a biomarker or target for the diagnosis and treatment of ccRCC.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales Límite: Humans Idioma: En Revista: FEBS Open Bio Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales Límite: Humans Idioma: En Revista: FEBS Open Bio Año: 2023 Tipo del documento: Article País de afiliación: China