Perspectives of lipid metabolism reprogramming in head and neck squamous cell carcinoma: An overview

Miao, Xiangwan; Wang, Beilei; Chen, Kaili; Ding, Rui; Wu, Jichang; Pan, Yi-Ru; Ji, Peilin; Ye, Bin; Xiang, Ming

doi:10.3389/fonc.2022.1008361

Cited by 13 publications

(8 citation statements)

References 138 publications

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“…In this context, the upregulation we observed for apolipoproteins (APOs) and fatty acid desaturase (FADS) gene families remarked the role of lipid profiles in HNSCC [ 72 , 73 ]. However, we did not appreciate this for the carbohydrate or glutamine metabolism, as reported in other studies [ 74 ].…”

Section: Discussionmentioning

confidence: 70%

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

Arfin,

Kumar,

Lomagno

et al. 2023

Cancers

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Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we hereby propose a retrospective in silico study to shed light on gene–miRNA interactions driving the development of HNSCC. Moreover, to identify topological biomarkers as a source for designing new drugs. To achieve this, gene and miRNA profiles from patients and controls are holistically reevaluated using protein–protein interaction (PPI) and bipartite miRNA–target networks. Cytoskeletal remodeling, extracellular matrix (ECM), immune system, proteolysis, and energy metabolism have emerged as major functional modules involved in the pathogenesis of HNSCC. Of note, the landscape of our findings depicts a concerted molecular action in activating genes promoting cell cycle and proliferation, and inactivating those suppressive. In this scenario, genes, including VEGFA, EMP1, PPL, KRAS, MET, TP53, MMPs and HOXs, and miRNAs, including mir-6728 and mir-99a, emerge as key players in the molecular interactions driving HNSCC tumorigenesis. Despite the heterogeneity characterizing these HNSCC subtypes, and the limitations of a study pointing to relationships that could be context dependent, the overlap with previously published studies is encouraging. Hence, it supports further investigation for key molecules, both those already and not correlated to HNSCC.

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Section: Discussionmentioning

confidence: 70%

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

Arfin,

Kumar,

Lomagno

et al. 2023

Cancers

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“…Circulating tumor cells, using CAMs present on their surface to adhere to the endothelium, exited the vasculature with strong blood ow impact force by extravasation, forming metastases at a distance [48]. It has been found that lipid metabolism was reprogrammed in cancer [49] and also played a crucial role in HNSCC [50]. Lipid metabolism supported the survival, proliferation, invasion, and metastasis of cancer cells by promoting membrane formation, energy production, signal transduction, and even mediating drug resistance [51,52].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel ceRNA networks associated with PD- L1 in head and neck squamous cell carcinoma based on whole-transcriptome sequencing

Han

Sun

et al. 2023

Preprint

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Objective Head and neck squamous cell carcinoma (HNSCC) is a common and fatal cancer type worldwide. Competing endogenous RNA (ceRNA) plays an important role in tumor development and progression through circular RNAs (circRNAs). Therefore, in this study, we attempted to explore the mechanisms by which circRNA/miRNA/mRNA ceRNA networks regulate head and neck squamous cell carcinoma HNSCC. Methods The biopsy samples from patients with HNSCC were obtained intra-operatively before any therapeutic intervention. The expression profiles of circRNAs, miRNAs, and mRNAs were performed using whole-transcriptome resequencing. Then, significantly differentially expressed circRNAs, miRNAs and mRNAs were screened out. The circRNA/miRNA/mRNA ceRNA networks were constructed based on the predicted circRNA–miRNA interactions and miRNA–mRNA interactions. After that, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to elucidate the possible functions of mRNAs contained in the ceRNA network. Furthermore, the hub network was screened among the key pathways of enrichment analysis. Finally, the expression of RNAs in hub network were verified by QRT-PCR and the association between them was revealed by Spearman correlation analysis. Results A total of 421 circRNAs, 112 miRNAs, and 1074 mRNAs with differential expression were detected. Among these, the top 9 circRNAs, 28 miRNAs, and 334 mRNAs were screened to construct a ceRNA network. The KEGG signal pathway and GO enrichment analysis of 334 mRNAs showed that cell adhesion molecules (CAMs), amino acid metabolism and other related pathways, biological processes such as extracellular matrix histogenesis were significantly enriched. Among them, CD274 and other genes were mainly enriched in CAMs pathway. Ultimately, a subnetwork including hsa_circ_0044507, hsa_circ_0044517, hsa_circ_0026774, hsa-miR-4446-3p, and PD-L1 (CD274) was screened out. QRT-PCR validated that the expression of hsa_circ_0044507, hsa_circ_0044517, hsa_circ_0026774, and PD-L1 were significantly increased, and hsa-miR-4446-3p were expressed significantly less in tumor tissue than in adjacent tissue. Spearman correlation showed that the expression of hsa_circ_0044507, hsa_circ_0044517, hsa_circ_0026774 were negatively correlated with hsa-miR-4446-3p, and positively correlated with PD-L1. Conclusion CeRNA network including hsa_circ_0044507, hsa_circ_0044517, hsa_circ_0026774, hsa-miR-4446-3p, and PD-L1 may be key regulators for HNSCC, and may be potential targets for the pathogenesis and treatment development of HNSCC.

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“…Over the last decade, it has become increasingly clear that changes in lipid metabolism are commonly associated with advanced, treatment-resistant carcinomas [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. There is extensive evidence for ongoing redesign of lipid metabolism in tumor cells as they progress to more advanced, treatment-resistant carcinoma [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Moreover, hypoxia, commonly experienced by carcinoma cells in vivo and representing a negative clinical prognostic, upregulates fatty acid uptake and storage [ 37 , 38 , 39 ].…”

Section: Context Of “Lipid Metabolism Resistance System” (Lmrs) Hypot...mentioning

confidence: 99%

Toward a Unifying Hypothesis for Redesigned Lipid Catabolism as a Clinical Target in Advanced, Treatment-Resistant Carcinomas

Bingham,

Zachar

2023

IJMS

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We review extensive progress from the cancer metabolism community in understanding the specific properties of lipid metabolism as it is redesigned in advanced carcinomas. This redesigned lipid metabolism allows affected carcinomas to make enhanced catabolic use of lipids in ways that are regulated by oxygen availability and is implicated as a primary source of resistance to diverse treatment approaches. This oxygen control permits lipid catabolism to be an effective energy/reducing potential source under the relatively hypoxic conditions of the carcinoma microenvironment and to do so without intolerable redox side effects. The resulting robust access to energy and reduced potential apparently allow carcinoma cells to better survive and recover from therapeutic trauma. We surveyed the essential features of this advanced carcinoma-specific lipid catabolism in the context of treatment resistance and explored a provisional unifying hypothesis. This hypothesis is robustly supported by substantial preclinical and clinical evidence. This approach identifies plausible routes to the clinical targeting of many or most sources of carcinoma treatment resistance, including the application of existing FDA-approved agents.

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Perspectives of lipid metabolism reprogramming in head and neck squamous cell carcinoma: An overview

Cited by 13 publications

References 138 publications

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

Identification of novel ceRNA networks associated with PD- L1 in head and neck squamous cell carcinoma based on whole-transcriptome sequencing

Toward a Unifying Hypothesis for Redesigned Lipid Catabolism as a Clinical Target in Advanced, Treatment-Resistant Carcinomas

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