The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors

Tong, Huan; He, Wei; Smith, Alhaji Osman; Huang, Juan

doi:10.3389/fimmu.2021.802049

Cited by 9 publications

(5 citation statements)

References 130 publications

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“…These include GC, HCC, CRC, NSCLC, SCLC, triple-negative breast cancer, urothelial carcinoma, melanoma, etc. [310][311][312][313][314][315][316][317][318][319][320][321][322]. Immune checkpoint inhibitors (ICIs) are designed to Fig.…”

Section: Targeting Rna Methylation Enhances the Therapeutic Effects O...mentioning

confidence: 99%

The role of RNA methylation in tumor immunity and its potential in immunotherapy

Li,

Jin,

et al. 2024

Mol Cancer

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RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating RNA splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of RNA methylation on tumor immunity. The primary types of RNA methylation encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G), and 3-methylcytidine (m3C). Compelling evidence underscores the involvement of RNA methylation in regulating the tumor microenvironment (TME). By affecting RNA translation and stability through the "writers", "erasers" and "readers", RNA methylation exerts influence over the dysregulation of immune cells and immune factors. Consequently, RNA methylation plays a pivotal role in modulating tumor immunity and mediating various biological behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed the mechanisms and functions of several RNA methylations, providing a comprehensive overview of their biological roles and underlying mechanisms within the tumor microenvironment and among immunocytes. By exploring how these RNA modifications mediate tumor immune evasion, we also examine their potential applications in immunotherapy. This review aims to provide novel insights and strategies for identifying novel targets in RNA methylation and advancing cancer immunotherapy efficacy.

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Section: Targeting Rna Methylation Enhances the Therapeutic Effects O...mentioning

confidence: 99%

The role of RNA methylation in tumor immunity and its potential in immunotherapy

Li,

Jin,

et al. 2024

Mol Cancer

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“…Early screening can effectively curb the development of CRC, but a large number of patients in China are still diagnosed with advanced CRC. Immune checkpoint blockade (ICB) shows promise in treating advanced CRC ( 13 ), but drug resistance remains a challenge ( 14 ), contributing to a high mortality rate. Therefore, developing new immunotherapy targets to improve the survival rate of CRC patients is currently the top priority.…”

Section: Introductionmentioning

confidence: 99%

Construction of a new prognostic model for colorectal cancer based on bulk RNA-seq combined with The Cancer Genome Atlas data

Ye,

2024

Transl Cancer Res

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Background Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths, and improving the prognosis of CRC patients is an urgent concern. The aim of this study was to explore new immunotherapy targets to improve survival in CRC patients. Methods We analyzed CRC-related single-cell data GSE201348 from the Gene Expression Omnibus (GEO) database, and identified differentially expressed genes (DEGs). Subsequently, we performed differential analysis on the rectum adenocarcinoma (READ) and colon adenocarcinoma (COAD) transcriptome sequencing data [The Cancer Genome Atlas (TCGA)-CRC queue] and clinical data downloaded from TCGA database. Subgroup analysis was performed using CIBERSORTx and cluster analysis. Finally, biomarkers were identified by one-way cox regression as well as least absolute shrinkage and selection operator (LASSO) analysis. Results In this study, we analyzed CRC-related single-cell data GSE201348, and identified 5,210 DEGs. Subsequently, we performed differential analysis on the TCGA-CRC queue database, and obtained 4,408 DEGs. Then, we categorized the cancer samples in the sequencing data into three groups (k1, k2, and k3), with significant differences observed between the k1 and k2 groups via survival analysis. Further differential analysis on the samples in the k1 and k2 groups identified 1,899 DEGs. A total of 77 DEGs were selected among those DEGs obtained from three differential analyses. Through subsequent Cox univariate analysis and LASSO analysis, seven biomarkers ( RETNLB , CLCA4 , UGT2A3 , SULT1B1 , CCL24 , BMP5 , and ATOH1 ) were identified and selected to establish a risk score (RS). Conclusions To sum up, this study demonstrates the potential of the seven-gene prognostic risk model as instrumental variables for predicting the prognosis of CRC.

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“…ICIs, mainly targeting CTLA4, PD-1, and PD-L1, has achieved remarkable success in the past decades, which has improved the outcomes of patients with advanced-stage cancer. Despite the therapeutic success achieved in the combination of ICIs with other therapies, many patients might not respond or have a low response to current treatment, thus, drug resistance and relapses are common treatment difficulties found nowadays ( 46 , 121 ). The lack of responsiveness demonstrates a clear need to outline the underlying mechanisms of tumor ICIs for the treatment of tumors.…”

Section: Introductionmentioning

confidence: 99%

Roles and therapeutic implications of m6A modification in cancer immunotherapy

et al. 2023

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Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), and m6A recognition proteins (readers). Aberrant regulation of m6A modification is pivotal for tumorigenesis, progression, invasion, metastasis, and apoptosis of malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized by the 2018 Nobel Prize in Medicine and Physiology. However, not all cancer patients response to ICI therapy, which is thought to be the result of intricate immune escape mechanisms. Recently, numerous studies have suggested a novel role for m6A epigenetic modification in the regulation of tumor immune evasion. Herein, we review the relevant mechanisms of m6A regulators in regulating various key signaling pathways in cancer biology and how m6A epigenetic modifications regulate the expression of immune checkpoints, opening a new window to understand the roles and mechanisms of m6A epigenetic modifications in regulating tumor immune evasion. In addition, we highlight the prospects and development directions of future combined immunotherapy strategies based on m6A modification targeting, providing directions for promoting the treatment outcomes of immune checkpoint inhibitors.

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The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors

Cited by 9 publications

References 130 publications

The role of RNA methylation in tumor immunity and its potential in immunotherapy

The role of RNA methylation in tumor immunity and its potential in immunotherapy

Construction of a new prognostic model for colorectal cancer based on bulk RNA-seq combined with The Cancer Genome Atlas data

Roles and therapeutic implications of m6A modification in cancer immunotherapy

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