<scp>HNRNPC</scp> suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer

Cheng, Yifei; Li, Lü; Wei, Xiyi; Xu, Fan; Huang, Xiaochen; Qi, Feng; Zhang, Yanyan; Li, Xiao

doi:10.1111/cas.15745

Cited by 14 publications

(4 citation statements)

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“…Increasing studies have revealed the m 6 A regulatory patterns of PCa and correlated these modification patterns with the tumor immune cell infiltration microenvironment characteristics ( 49 – 51 ). In addition, a recent paper found that m 6 A reader HNRNPC can regulate Treg cell abundance as a possible mechanism for m 6 A methylation-mediated response against CTLA-4, indicating that activation of the immune microenvironment by targeting m 6 A regulators may serve as a potential therapeutic approach for advanced PCa( 52 ).Our study synthetically analyzed the relationship between the expression of m 6 A regulators and immune characteristics and drug sensitivity of PCa patients. In accordance with the previous reports, we confirmed that resting memory CD4+ T cells and Tregs are highly correlated with m 6 A-related genes ( 53 , 54 ), while both high- and low-risk groups are sensitive to a number of therapeutic drugs.…”

Section: Discussionmentioning

confidence: 92%

The m6A methylation landscape, molecular characterization and clinical relevance in prostate adenocarcinoma

Peng

Gan

et al. 2023

Front. Immunol.

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BackgroundDespite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6-methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance.MethodsThrough systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6A-related genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups.ResultsA variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased.ConclusionsThis study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs.

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Section: Discussionmentioning

confidence: 92%

The m6A methylation landscape, molecular characterization and clinical relevance in prostate adenocarcinoma

Peng

Gan

et al. 2023

Front. Immunol.

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“…On the other hand, a previous study demonstrated the correlation between m6A methylation and immune cell infiltration in PCa [33]. Another study has shown that HNRNPC may activate the immune-suppressive tumor microenvironment by promoting PCa progression [53]. Hence, it is noteworthy to study the therapeutic potential of targeting upstream m6A regulators to activate the immune microenvironment in PCa.…”

Section: Discussionmentioning

confidence: 99%

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations

Liyanage,

Fernando,

Chamberlain

et al. 2024

Cancers

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N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays a crucial role in regulating mRNA expression, stability, and translation in mammals. M6A regulators have gained attention for their potential implications in tumorigenesis and clinical applications, such as cancer diagnosis and therapeutics. The existing literature predominantly addresses m6A regulators in the context of primary prostate cancer (PCa). However, a notable gap in the knowledge emerges regarding the dynamic expression patterns of these regulators as PCa progresses towards the castration-resistant stage (CRPC). Employing sequential window acquisition of all theoretical mass spectra (SWATH-MS) and RNAseq analysis, we comprehensively profiled the expression of 27 m6A regulators in hormone/androgen-dependent and -independent PCa cell lines, revealing distinct clustering between tumor and adjacent normal prostate tissues. High-grade PCa tumors demonstrated the upregulation of METTL3, RBM15B, and HNRNAPA2B1 and the downregulation of ZC3H13, NUDT21, and FTO. Notably, we identified six m6A regulators associated with PCa survival. Additionally, association analysis of the PCa-associated risk loci in the cancer genome atlas program (TCGA) data unveiled genetic variations near the WTAP, HNRNPA2B1, and FTO genes as significant expression quantitative trait loci. In summary, our study unraveled abnormalities in m6A regulator expression in PCa progression, elucidating their association with PCa risk loci. Considering the heterogeneity within the PCa phenotypes and treatment responses, our findings suggest that prognostic stratification based on m6A regulator expression could enhance PCa diagnosis and prognosis.

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“…However, Li et al. reported that HNRNPC regulated the activation of Treg cells by activating the immune microenvironment, which may be a potential therapeutic target for prostate cancer ( 35 ). In pancreatic cancer, HNRNPC induced DNA damage repair and cancer-associated fibroblast activation through the RhoA/ROCK2-YAP/TAZ signaling pathway ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine with immune infiltration and PD-L1 in hepatocellular carcinoma: novel perspective to personalized diagnosis and treatment

et al. 2023

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BackgroundIncreasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators and the immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC).MethodsTotals of 371 HCC and 50 normal patients were included in this study. GSE121248 and GSE40367 datasets were used to validate the expression of HNRNPC. The R package “ConsensusClusterPlus” was performed to screen consensus clustering types based on the expression of m6A regulators in HCC. The R package “pheatmap”, “immunedeconv”, “survival”, “survminer” and “RMS” were applied to investigate the expression, immunity, overall survival, and clinical application in different clusters and expression groups. Comprehensive analysis of HNRNPC in pan-cancer was conducted by TIMER2 database. Besides, HNRNPC mRNA and protein expression were verified by qRT-PCR and immunohistochemistry analysis.ResultsMost of m6A regulators were over-expressed excerpt for ZC3H13 in HCC. Three independent clusters were screened based on m6A regulators expression, and the cluster 2 had a favorable prognosis in HCC. Then, the cluster 2 was positively expression in macrophage, hematopoietic stem cell, endothelial cell, and stroma score, while negatively in T cell CD4+ memory and mast cell. We identified HNRNPC was an independent prognostic factor in HCC, and nomogram performed superior application value for clinical decision making. Moreover, PD-L1 was significantly up-regulated in HCC tissues, cluster 1, and cluster 3, and we found PD-L1 expression was positively correlated with HNRNPC. Patients with HCC in high-expression groups was associated with tumor-promoting cells. Besides, HNRNPC was correlated with prognosis, TMB, and immune checkpoints in cancers. Particularly, the experiments confirmed that HNRNPC was positively expression in HCC cells and tissues.ConclusionThe m6A regulators play irreplaceable roles in prognosis and immune infiltration in HCC, and the relationship of HNRNPC and PD-L1 possesses a promising direction for therapeutic targets of immunotherapy response. Exploration of m6A regulators pattern could be build the prognostic stratification of individual patients and move toward to personalized treatment.

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HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer

Cited by 14 publications

References 58 publications

The m6A methylation landscape, molecular characterization and clinical relevance in prostate adenocarcinoma

The m6A methylation landscape, molecular characterization and clinical relevance in prostate adenocarcinoma

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations

N6-methyladenosine with immune infiltration and PD-L1 in hepatocellular carcinoma: novel perspective to personalized diagnosis and treatment

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