Abstract
Elevated lipid metabolism promotes cancer cell proliferation. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers, characterized by ectopic lipid accumulation. However, the relationship between aberrant lipid metabolism and tumorigenesis in ccRCC is not thoroughly understood. Here, we demonstrate that ring finger protein 20 (RNF20) acts as a tumor suppressor in ccRCC. RNF20 overexpression repressed lipogenesis and cell proliferation by inhibiting sterol regulatory element-binding protein 1c (SREBP1c), and SREBP1 suppression, either by knockdown or by the pharmacological inhibitor betulin, attenuated proliferation and cell cycle progression in ccRCC cells. Notably, SREBP1c regulates cell cycle progression by inducing the expression of pituitary tumor-transforming gene 1 (PTTG1), a novel target gene of SREBP1c. Furthermore, RNF20 overexpression reduced tumor growth and lipid storage in xenografts. In ccRCC patients, RNF20 downregulation and SREBP1 activation are markers of poor prognosis. Therefore, RNF20 suppresses tumorigenesis in ccRCC by inhibiting the SREBP1c-PTTG1 axis.
Highlights
Elevated lipid metabolism promotes cancer cell proliferation
Since ring finger protein 20 (RNF20) acts as a negative regulator of de novo lipogenesis by inhibiting sterol regulatory element-binding protein 1c (SREBP1c) [11], we investigated whether RNF20 might be dysregulated in Clear cell renal cell carcinoma (ccRCC) tumors
RNA sequencing (RNA-seq) data from the Cancer Genome Atlas (TCGA) revealed significant reductions in RNF20 mRNA expression in ccRCC tumors (Fig. 1B) and indicated that low RNF20 expression is closely correlated with advanced tumor stages (Fig. 1C)
Summary
Elevated lipid metabolism promotes cancer cell proliferation. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers, characterized by ectopic lipid accumulation. Ring finger protein 20 (RNF20) is an E3 ubiquitin ligase that plays various roles in transcription regulation, DNA damage responses, stem cell differentiation, and lipid metabolism [11,12,13]. It promotes the monoubiquitination of histone H2B, which regulates the transcription of a subset of genes and contributes to chromatin remodeling [13, 14]. SREBP1c-mediated lipogenic activation promotes tumor development, progression, and migration, leading to poor prognosis in several cancers [24, 25]. It is well known that lipid metabolic pathways are dysregulated in ccRCC [26, 27], the underlying mechanisms that lead to aberrant lipogenesis and cell proliferation in ccRCC remain poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
