Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning

Li, Xiangyu; Kim, Woonghee; Juszczak, Kajetan; Arif, Muhammad; Sato, Yusuke; Kume, Haruki; Ogawa, Seishi; Türkez, Hasan; Borén, Jan; Nielsen, Jens; Uhlén, Mathias; Zhang, Cheng Cheng; Mardinoğlu, Adil

doi:10.1016/j.isci.2021.102722

Cited by 9 publications

(11 citation statements)

References 66 publications

(102 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the genes involved in M4 from the Japanese cohort were enriched in the fatty acid metabolic process. In our previous study, we have reported three molecular subtypes of ccRCC characterized by the different activity of energy metabolism in terms of cell viability and proliferation, cell differentiation and fatty acid metabolism, 14 which are consistent with the functions of the modules we identified in this study. The genes involved in M5 from the Japanese cohort were significantly enriched in the translational initiation, protein targeting to the endoplasmic reticulum, protein targeting to membrane, viral transcription and viral gene expression pathways.…”

Section: Resultssupporting

confidence: 91%

“…Interestingly, two of the three subtypes we identified in our previous study were characterized by the opposite dysregulation of these pathways, corresponding to patients' best and poorest survival outcomes. 14 …”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we identified a list of candidate target genes which are essential for the ccRCC tumor cell growth by the genome-scale metabolic model analysis. 14 Among these essential genes, we further filtered out three genes, SOAT1, CRLS1 and ACACB , whose inhibition is not toxic in the 32 major normal human tissues by performing an in silico toxicity test for each essential gene, as the final targetable genes. Finally, we repurposed a well-known inhibitor of SOAT1 , mitotane, and validated its drug efficacy for the treatment of ccRCC.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach

Shong

Kim

et al. 2022

eBioMedicine

Self Cite

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach

Shong

Kim

et al. 2022

eBioMedicine

Self Cite

View full text Add to dashboard Cite

“…These subtypes have different frequencies of genetic mutation and levels of DNA promoter methylation based on an integrated multi-omics analysis. Recently, Li et al identified three subtypes of ccRCC with different prognoses, and identified a set of biomarkers that could robustly stratify the patients into different subtypes using the relative expression orders of biomarker genes [74].…”

Section: Kidney Cancermentioning

confidence: 99%

“…In recent years, the anticancer effects of repurposed drugs have gained significant interest due to the lack of directed treatments for life-threatening cancers [8,74,81]. Drug repurposing applications combine diverse approaches by complementing experimental and computational methodologies to discover targets in the fight against various cancers, including GBM [82].…”

Section: Drug Repositioning Applications In Gbmmentioning

confidence: 99%

Systems Biology Approaches to Decipher the Underlying Molecular Mechanisms of Glioblastoma Multiforme

Kaynar

Altay

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is one of the most malignant central nervous system tumors, showing a poor prognosis and low survival rate. Therefore, deciphering the underlying molecular mechanisms involved in the progression of the GBM and identifying the key driver genes responsible for the disease progression is crucial for discovering potential diagnostic markers and therapeutic targets. In this context, access to various biological data, development of new methodologies, and generation of biological networks for the integration of multi-omics data are necessary for gaining insights into the appearance and progression of GBM. Systems biology approaches have become indispensable in analyzing heterogeneous high-throughput omics data, extracting essential information, and generating new hypotheses from biomedical data. This review provides current knowledge regarding GBM and discusses the multi-omics data and recent systems analysis in GBM to identify key biological functions and genes. This knowledge can be used to develop efficient diagnostic and treatment strategies and can also be used to achieve personalized medicine for GBM.

show abstract

Multi-tissue network analysis reveals the effect of JNK inhibition on dietary sucrose-induced metabolic dysfunction in rats

Yang,

Zhang,

Kim

et al. 2024

Preprint

View full text Add to dashboard Cite

Excessive consumption of sucrose, in the form of sugar-sweetened beverages, has been implicated in the pathogenesis of metabolic dysfunction?associated fatty liver disease (MAFLD) and other related metabolic syndromes. The c-Jun N-terminal kinase (JNK) pathway plays a crucial role in response to dietary stressors, and it was demonstrated that the inhibition of the JNK pathway could potentially be used in the treatment of MAFLD. However, the intricate mechanisms underlying these interventions remain incompletely understood given their multifaceted effects across multiple tissues. In this study, we challenged rats with sucrose-sweetened water and investigated the potential effects of JNK inhibition by employing network analysis based on the transcriptome profiling obtained from hepatic and extrahepatic tissues, including visceral white adipose tissue, skeletal muscle, and brain. Our data demonstrate that JNK inhibition by JNK-IN-5A effectively reduces the circulating triglyceride accumulation and inflammation in rats subjected to sucrose consumption. Coexpression analysis and genome-scale metabolic modelling reveal that sucrose overconsumption primarily induces transcriptional dysfunction related to fatty acid and oxidative metabolism in the liver and adipose tissues, which are largely rectified after JNK inhibition at a clinically relevant dose. Skeletal muscle exhibited minimal transcriptional changes to sucrose overconsumption but underwent substantial metabolic adaptation following the JNK inhibition. Overall, our data provides novel insights into the molecular basis by which JNK inhibition exerts its metabolic effect in the metabolically active tissues. Furthermore, our findings underpin the critical role of extrahepatic metabolism in the development of diet-induced steatosis, offering valuable guidance for future studies focused on JNK-targeting for effective treatment of MAFLD.

show abstract

Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning

Cited by 9 publications

References 66 publications

Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach

Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach

Systems Biology Approaches to Decipher the Underlying Molecular Mechanisms of Glioblastoma Multiforme

Multi-tissue network analysis reveals the effect of JNK inhibition on dietary sucrose-induced metabolic dysfunction in rats

Contact Info

Product

Resources

About