Dataset Information

PPAR? is dispensable for clear cell renal cell carcinoma progression.

ABSTRACT:

Objective

Clear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPAR?), detected in both ccRCC tumors and cell lines, promotes lipid storage in ccRCC and contributes to tumorigenesis in this setting. PPAR? transcriptionally regulates a number of genes involved in lipid and glucose metabolism in adipocytes, yet its role in ccRCC has not been described. The objective of this study was to elucidate endogenous PPAR? function in ccRCC cells.

Methods and results

Using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq), we found that PPAR? and its heterodimer RXR occupy the canonical DR1 PPAR binding motif at approximately 1000 locations throughout the genome that can be subdivided into adipose-shared and ccRCC-specific sites. CRISPR-Cas9 mediated, loss-of-function studies determined that PPAR? is dispensable for viability, proliferation, and migration of ccRCC cells in vitro and in vivo. Also, surprisingly, PPAR? deletion had little effect on the robust lipid accumulation that typifies the "clear cell" phenotype of kidney cancer.

Conclusion

Our results suggest that PPAR? plays neither a tumor suppressive nor oncogenic role in advanced ccRCC, and thus single-agent therapeutics targeting PPAR? are unlikely to be effective for the treatment of this disease. The unique cistrome of PPAR? in ccRCC cells demonstrates the importance of cell type in determining the functions of PPAR?.

SUBMITTER: Sanchez DJ

PROVIDER: S-EPMC6034040 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

PPARγ is dispensable for clear cell renal cell carcinoma progression.

Sanchez Danielle J DJ Steger David J DJ Skuli Nicolas N Bansal Ankita A Simon M Celeste MC

Molecular metabolism 20180521

<h4>Objective</h4>Clear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPARγ), detected in both ccRCC tumors and cell lines, promotes lipid storage in ccRCC and contributes to tumorigenesis in this setting. PPARγ transcriptionally regulates a number of genes involved in lipid and glucose ...[more]

PMID: 29866440

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