Integrated analysis of transcriptomics, proteomics and metabolomics data reveals the role of SLC39A1 in renal cell carcinoma

Yuan, Yuexing; Liu, Zimeng; Li, Bohan; Gong, Zheng; Piao, Chiyuan; Du, Yang; Zhan, Bo; Zhang, Zhe; Dong, Xiao

doi:10.3389/fcell.2022.977960

Cited by 3 publications

(3 citation statements)

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“…PPARs regulate cancer cell progression through crosstalk with oncogenes or suppressor genes [41]. Previous study showed that SLC39A1 impaired tumor metabolism and regulated ell proliferation, migration, and cell cycle through the PPAR crosstalk regulation in renal cell carcinoma (RCC) [42]. In our research, we investigated the crosstalk between PPARs and SLC27A2, and found non-genic crosstalk regulation of PPARs through p-Erk/Erk and p-GSK3β/GSK3β to influence FA metabolic reprogramming in CRC.…”

Section: Discussionmentioning

confidence: 84%

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

Shang

Che

et al. 2023

BMC Cancer

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Background Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment. Methods Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein–protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRT‒PCR were performed to explore the mechanisms. Results SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)‒related genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3β/GSK3β were elevated through nongenic crosstalk regulation of the PPARs pathway. Conclusions SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.

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Section: Discussionmentioning

confidence: 84%

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

Shang

Che

et al. 2023

BMC Cancer

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“…Research on HCC has shown that SLC39A1 overexpression is linked to immune infiltration and promotes tumor progression ( Zhang et al, 2021 ). Yuan et al (2022) conducted a study to explore SLC39A1’s potential as a tumor suppressor in renal cell carcinoma (RCC) using integrated omics analyses. They found that SLC39A1 significantly impacts various metabolic pathways and triggers communication among multiple signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…They found that SLC39A1 significantly impacts various metabolic pathways and triggers communication among multiple signaling pathways. This research provides valuable insights into RCC development and the molecular changes induced by SLC39A1 ( Yuan et al, 2022 ). Furthermore, glioma tissues exhibit increased SLC39A1 expression, strongly associated with clinical features like grade, IDH mutation status, and 1p19q co-deletion status.…”

Section: Discussionmentioning

confidence: 99%

Integrating bulk and single-cell RNA sequencing data reveals epithelial-mesenchymal transition molecular subtype and signature to predict prognosis, immunotherapy efficacy, and drug candidates in low-grade gliomas

Wang,

2023

Front. Pharmacol.

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Objective: Epithelial-mesenchymal transition (EMT) is a tightly regulated and dynamic process occurring in both embryonic development and tumor progression. Our study aimed to comprehensively explore the molecular subtypes, immune landscape, and prognostic signature based on EMT-related genes in low-grade gliomas (LGG) in order to facilitate treatment decision-making and drug discovery.Methods: We curated EMT-related genes and performed molecular subtyping with consensus clustering algorithm to determine EMT expression patterns in LGG. The infiltration level of diverse immune cell subsets was evaluated by implementing the single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms. The distinctions in clinical characteristics, mutation landscape, and immune tumor microenvironment (TME) among the subtypes were subjected to further investigation. Gene Set Variation Analysis (GSVA) was performed to explore the biological pathways that were involved in subtypes. The chemo drug sensitivity and immunotherapy of subtypes were estimated through GDSC database and NTP algorithm. To detect EMT subtype-related prognostic gene modules, the analysis of weighted gene co-expression network (WGCNA) was performed. The LASSO algorithm was utilized to construct a prognostic risk model, and its efficacy was verified through an independent CGGA dataset. Finally, the expression of the hub genes from the prognostic model was evaluated through the single-cell dataset and in-vitro experiment.Results: The TCGA-LGG dataset revealed the creation of two molecular subtypes that presented different prognoses, clinical implications, TME, mutation landscapes, chemotherapy, and immunotherapy. A three-gene signature (SLC39A1, CTSA and CLIC1) based on EMT expression pattern were established through WGCNA analysis. Low-risk patients showed a positive outlook, increased immune cell presence, and higher expression of immune checkpoint proteins. In addition, several promising drugs, including birinapant, fluvastatin, clofarabine, dasatinib, tanespimycin, TAK−733, GDC−0152, AZD8330, trametinib and ingenol-mebutate had great potential to the treatment of high risk patients. Finally, CTSA and CLIC1 were highly expressed in monocyte cell through single-cell RNA sequencing analysis.Conclusion: Our research revealed non-negligible role of EMT in the TME diversity and complexity of LGG. A prognostic signature may contribute to the personalized treatment and prognostic determination.

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Peroxisome biogenesis and inter-organelle communication: an indispensable role for Pex11 and Pex30 family proteins in yeast

Deori

Nagotu

2022

Curr Genet

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Integrated analysis of transcriptomics, proteomics and metabolomics data reveals the role of SLC39A1 in renal cell carcinoma

Cited by 3 publications

References 55 publications

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

Integrating bulk and single-cell RNA sequencing data reveals epithelial-mesenchymal transition molecular subtype and signature to predict prognosis, immunotherapy efficacy, and drug candidates in low-grade gliomas

Peroxisome biogenesis and inter-organelle communication: an indispensable role for Pex11 and Pex30 family proteins in yeast

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