Alteration of CYP4A11 expression in renal cell carcinoma: diagnostic and prognostic implications

Kim, Sup; Kim, Jin Man; Lim, Jae Sung; Seong, In-Ock; Kim, Kyung‐Hee

doi:10.7150/jca.36438

Cited by 13 publications

(6 citation statements)

References 24 publications

(34 reference statements)

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“…In this study, based on our cohort of 52 paired ccRCC tumor tissues and matched adjacent non-tumor tissues, we showed the overexpression of miR-21 in ccRCC as well as an inverse correlation between miR-21 and PPAR-α expression. Consistent with Kim et al [33], we also showed that the PPAR-α protein level was barely detectable in most ccRCC clinical samples, suggesting that miR-21 may influence PPAR-α expression and consequently its activity. As PPAR-α is a bona fide target of miR-21, we performed a series of experiments aiming to better characterize the regulatory mechanism shared by miR-21, PPAR-α, and lipid metabolism in ccRCC.…”

Section: Discussionsupporting

confidence: 91%

A Double-Negative Feedback Interaction between miR-21 and PPAR-α in Clear Renal Cell Carcinoma

Goujon

Woszczyk

Gaudelot

et al. 2022

Cancers

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Clear cell renal cell carcinoma (ccRCC) is the main histotype of kidney cancer, which is typically highly resistant to conventional therapies and known for abnormal lipid accumulation. In this context, we focused our attention on miR-21, an oncogenic miRNA overexpressed in ccRCC, and peroxysome proliferator-activated receptor-α (PPAR- α), one master regulator of lipid metabolism targeted by miR-21. First, in a cohort of 52 primary ccRCC samples, using RT-qPCR and immunohistochemistry, we showed that miR-21 overexpression was correlated with PPAR-α downregulation. Then, in ACHN and 786-O cells, using RT-qPCR, the luciferase reporter gene, chromatin immunoprecipitation, and Western blotting, we showed that PPAR-α overexpression (i) decreased miR-21 expression, AP-1 and NF-κB transcriptional activity, and the binding of AP-1 and NF-κB to the miR-21 promoter and (ii) increased PTEN and PDCD4 expressions. In contrast, using pre-miR-21 transfection, miR-21 overexpression decreased PPAR-α expression and transcriptional activity mediated by PPAR-α, whereas the anti-miR-21 (LNA-21) strategy increased PPAR-α expression, but also the expression of its targets involved in fatty acid oxidation. In this study, we showed a double-negative feedback interaction between miR-21 and PPAR-α. In ccRCC, miR-21 silencing could be therapeutically exploited to restore PPAR-α expression and consequently inhibit the oncogenic events mediated by the aberrant lipid metabolism of ccRCC.

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Section: Discussionsupporting

confidence: 91%

A Double-Negative Feedback Interaction between miR-21 and PPAR-α in Clear Renal Cell Carcinoma

Goujon

Woszczyk

Gaudelot

et al. 2022

Cancers

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“…In recent years, with the development of molecular biology technology and bioinformatics, new biomarkers have the potential to be used as prognostic factors for different types of cancer, including pRCC. For instance, some studies have found that CYP4A11 expression is a potential poor prognostic factor for RCC [8], while others have detected long noncoding RNAs that might serve as prognostic biomarkers for pRCC [9], and some alternative splicing events also correlate with pRCC prognosis [10]. Therefore, finding new molecular markers to predict the clinical outcome of pRCC is of great significance for understanding pRCC's molecular pathological characteristics, prognosis, and treatment.…”

Section: Introductionmentioning

confidence: 99%

Identification of methylation-driven genes related to the prognosis of papillary renal cell carcinoma: a study based on The Cancer Genome Atlas

et al. 2020

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Background: Aberrant DNA methylation patterns are involved in the pathogenesis of papillary renal cell carcinoma (pRCC). This study aimed to investigate the potential of methylation-driven genes as biomarkers in determining the prognosis of pRCC by bioinformatics analysis. Methods: DNA methylation and transcriptome profiling data were downloaded from The Cancer Genome Atlas database. Methylation-driven genes (MDGs) were obtained using MethylMix R package. A Cox regression model was used to screen for pRCC prognosis-related MDGs, and a linear risk model based on MDG methylation profiles was constructed. A combined methylation and gene expression survival analysis was performed to further explore the prognostic value of MDGs independently. Results: A total of 31 MDGs were obtained. Univariate and multivariate Cox regression analysis identified eight genes (CASP1, CD68, HOXD3, HHLA2, HOXD9, HOXA10-AS, TMEM71, and PLA2G16), which were used to construct a predictive model associated with overall survival in pRCC patients. Combined DNA methylation and gene expression survival analysis revealed that C19orf33, GGT6, GIPC2, HHLA2, HOXD3, HSD17B14, PLA2G16, and TMEM71 were significantly associated with patients' survival. Conclusion: Through the analysis of MDGs in pRCC, this study identified potential biomarkers for precision treatment and prognosis prediction, and provided the basis for future research into the molecular mechanism of pRCC.

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“…CYP4A11, a member of CYP4 family, is involved in fatty acid metabolism. It is decreased in tumor tissues such as hepatocellular carcinoma, 21 renal cell carcinoma, 22 and lung cancer 5 . PGM2 is an alpha‐phosphate glucose mutase.…”

Section: Discussionmentioning

confidence: 99%

Construction of a prognostic model based on genes associated with mitochondrial energy metabolic pathway in colon adenocarcinoma and its clinical significance

Zhang

Liang

Zhou

et al. 2023

J of Molecular Recognition

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Mitochondria are the main sites of oxidative metabolism and energy release of sugars, fats and amino acids in the body. According to studies, malignant tumor occurrence and development have been linked to abnormal mitochondrial energy metabolism (MEM). However, the feasible role of abnormal MEM in colon adenocarcinoma (COAD) is poorly understood. In this work, we obtained COAD patient data from The Cancer Genome Atlas (TCGA) as the training set, and GSE103479 from Gene Expression Omnibus (GEO) as the validation set. Combined with the mitochondrial energy metabolic pathway (MEMP)-related genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) database, a risk prognostic model was constructed by utilizing Cox regression analysis to identify 6 feature genes (CYP4A11, PGM2, PKLR, PPARGC1A, CPT2 and ACAT2) that were significantly associated with MEMP in COAD. By stratifying the samples based on riskscore, two distinct groups, namely the high-and low-risk groups, were identified. The model demonstrated accurate assessment of the prognosis risk in COAD patients and exhibited independent prognostic capability, as evidenced by the survival curve and receiver operating characteristic (ROC) curve analysis. A nomogram was plotted based on clinical information and riskscore. We proved it could predict the survival time of COAD patients effectively combined with the calibration curve of risk prediction. Subsequently, based on the immune evaluation and mutation frequency analysis performed on COAD patients, patients in high-risk group had observably higher immune scores, immune activity and PDCD1 expression level than low-risk group. In general, the prognostic model developed using MEMP-related genes served as a valuable biomarker for forecasting the prognosis of COAD patients, which offered a reference for the prognosis evaluation and clinical cure of COAD patients.

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Alteration of CYP4A11 expression in renal cell carcinoma: diagnostic and prognostic implications

Cited by 13 publications

References 24 publications

A Double-Negative Feedback Interaction between miR-21 and PPAR-α in Clear Renal Cell Carcinoma

A Double-Negative Feedback Interaction between miR-21 and PPAR-α in Clear Renal Cell Carcinoma

Identification of methylation-driven genes related to the prognosis of papillary renal cell carcinoma: a study based on The Cancer Genome Atlas

Construction of a prognostic model based on genes associated with mitochondrial energy metabolic pathway in colon adenocarcinoma and its clinical significance

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