Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma

Wang, Can; Cui, Guoliang; Wang, Dan; Wang, Min; Chen, Qi; Wang, Yunshan; Lu, Mengjie; Tang, Xinyi; Yang, Bo‐Lin

doi:10.3390/cancers14184503

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…Next, we sought to investigate the molecular mechanism. In colorectal cancer, forty-two OXPHOS-related genes were differentially expressed between tumor and normal samples, with 8 genes showing prognostic value 39 . Combined with our sequencing data, we identified that one target, PPARGC1A , was significantly upregulated in recipient cells treated with Res-exos (Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer

Deng,

Pan,

et al. 2023

Theranostics

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Background: Recently years have seen the increasing evidence identifying that OXPHOS is involved in different processes of tumor progression and metastasis and has been proposed to be a potential therapeutical target for cancer treatment. However, the exploration in oxidative phosphorylation-mediated chemoresistance is still scarce. In our study, we identify exosomal transfer leads to chemoresistance by reprogramming metabolic phenotype in recipient cells. Methods: RNA sequencing analysis was used to screen altered targets mediating exosome transfer-induced chemoresistance. Seahorse assay allowed us to measure mitochondrial respiration. Stemness was measured by spheroids formation assay. Serum exosomes were isolated for circ_0001610 quantification. Results:The induced oxidative phosphorylation leads to more stem-like properties, which is dependent on the transfer of exosomal circ_0001610. Exosome transfer results in the removal of miR-30e-5p-mediated suppression of PGC-1a, a master of mitochondrial biogenesis and function. Consequently, increased PGC-1a reshapes cellular metabolism towards oxidative phosphorylation, leading to chemoresistance. Inhibition of OXPHOS or exosomal si-circ_0001610 increases the sensitivity of chemotherapy by decreasing cell stemness in vitro and in vivo. Conclusion: Our data suggests that exosomal circ_0001610-induced OXPHOS plays an important role in chemoresistance and supports a therapeutical potential of circ_0001610 inhibitors in the treatment of oxaliplatin-resistant colorectal cancer by manipulating cell stemness.

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Section: Resultsmentioning

confidence: 99%

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer

Deng,

Pan,

et al. 2023

Theranostics

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“…The "limma" software package was used to analyze the differentially expressed genes (DEGs) between the two m6A clusters with thresholds of |log2FC|≥ 1 and FDR ≤ 0.05. We used "clusterProfiler" to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses to explore the potential biological functions of these DEGs 28 .…”

Section: Methodsmentioning

confidence: 99%

Diagnostic, clustering, and immune cell infiltration analysis of m6A regulators in patients with sepsis

Zhang

Peng

et al. 2023

Sci Rep

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RNA N6-methladenosine (m6A) regulators are required for a variety of biological processes, including immune responses, and increasing evidence indicates that their dysregulation is closely associated with many diseases. However, the potential roles of m6A regulators in sepsis remain unknown. We comprehensively analyzed the transcriptional variations in and interactions of 26 m6A regulators in sepsis based on the Gene Expression Omnibus (GEO) database. A random forest (RF) model and nomogram were established to predict the occurrence and risk of sepsis in patients. Then, two different m6A subtypes were defined by consensus clustering analysis, and we explored the correlation between the subtypes and immune cells. We found that 17 of the 26 m6A regulators were significantly differentially expressed between patients with and without sepsis, and strong correlations among these 17 m6A regulators were revealed. Compared with the support vector machine (SVM) model, the RF model had better predictive ability, and therefore was used to construct a reliable nomogram containing 10 candidate m6A regulators to predict the risk of sepsis in patients. In addition, a consensus clustering algorithm was used to identify two different subtypes of m6A, which helped us distinguish different levels of immune cell infiltration and inflammation in patients with sepsis. Comprehensive analysis of m6A regulators in sepsis revealed their potential roles in sepsis occurrence, immune cell infiltration and inflammation in patients with sepsis. This study may contribute to the development of follow-up treatment strategies for sepsis.

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“… 224 In GBM, IGF2BP2 was involved in maintaining stability of SHMT2 mRNA, which played a crucial role in OXPHOS activities, as a significant driving force of GBM tumorigenesis. 350 Elevated m6A level and IGF2BP2 expression conduced to maintenance of hematopoietic stem cells (HSCs) via restricting mitochondrial activity. IGF2BP2 deficiency accelerated degradation of Bmi1 mRNA, relieving its depression on mitochondria-related genes, thus impaired quiescence state and functions of HSCs.…”

Section: Rna Modifications and Cellular Metabolismmentioning

confidence: 99%

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Liu,

Zheng,

et al. 2024

Sig Transduct Target Ther

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Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

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Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma

Cited by 5 publications

References 69 publications

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer

Diagnostic, clustering, and immune cell infiltration analysis of m6A regulators in patients with sepsis

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

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