AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma

Abstract

Lipid metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Lipid accumulation affects cellular energy homeostasis, biofilm synthesis, lipid signal transduction, and phenotypic transformation in ccRCC. Herein, a prognostic‐related model was constructed, and the prognostic utility of AUP1, a lipid droplet–regulating very low–density lipoprotein assembly factor, in ccRCC was determined through multiparameter analysis. AUP1 expression was significantly higher in clinical samples than in normal tissues and was closely associated with the clinical stage. The inhibition of AUP1 expression impaired the proliferation, migration, and invasion of ACHN and A498 ccRCC cells in vitro and in vivo. RNA‐seq analysis revealed that AUP1 inhibition can significantly reduce the contents of intracellular triglyceride and cholesterol and regulate cell growth by cell cycle arrest, promoting apoptosis and reversing epithelial‐mesenchymal transition. AUP1 regulated the synthesis of cholesterol esters and fatty acids (FAs) in ccRCC cells by targeting sterol O‐acyltransferase 1 and partially promoted the progression of ccRCC. AUP1 also induced lipid accumulation in ccRCC by promoting the de novo synthesis of FAs (inhibiting protein kinase AMP‐activated catalytic subunit alpha 2), inhibiting the rate‐limiting enzyme of FA β oxidation (carnitine palmitoyltransferase 1A), regulating the key enzyme of lipolysis (monoglyceride lipase, MGLL), and inhibiting the lipid transporter StAR‐related lipid transfer domain containing 5 (STARD5). However, it did not affect the intracellular cholesterol synthesis pathway. The differential expression and prognostic significance of MGLL and STARD5 in ccRCC should be further studied. AUP1 may serve as a new and effective potential target and prognostic marker for ccRCC.

Integrating single-cell analysis and machine learning to create glycosylation-based gene signature for prognostic prediction of uveal melanoma

“…AUP1 has an “ancient conserved area” in proteins from unrelated organisms ( 47 ). Due to its age and high level of sequence conservation, the protein encoded by AUP1 is essential for cell biology ( 48 ). However, the function of AUP1 in UM has yet to be determined.…”

Cellular communication through extracellular vesicles and lipid droplets

“…Proteins specific to LDs ADRP (PLIN) (Imamura et al, 2002;Yang, Ding, et al, 2012) • Assists in the storage of neutral lipids within the LDs (Imamura et al, 2002) PLIN (Itabe et al, 2017;Yang, Ding, et al, 2012) • Lipid metabolism (Hansen et al, 2017) AUP (Spandl et al, 2011) • Regulates lipid metabolism and induces lipid accumulation (Chen et al, 2022) BSCL (Seipin) (Salo et al, 2016) • Plays a crucial role in the formation of LDs, particularly budding from ER (Kim et al, 2022).…”

Metabolic classifications of renal cell carcinoma reveal intrinsic connections with clinical and immune characteristics

“…A well-known metabolic hallmark of clear cell renal cell carcinoma (ccRCC) is an aberrant accumulation of lipid and glycogen [ 9 ], which has been reported recently as a secondary and dispensable consequence of active HIF-1α signaling and disruption of glycogen synthesis did not affect tumor growth in murine models [ 10 ]. Lipid metabolic reprogramming, however, is believed to get involved in a series of micro and macro-level life activities including cellular energy homeostasis, biofilm synthesis, lipid signal transduction, and phenotypic transformation in RCC [ 11 ].…”