RNA N6-Methyladenosine in Cancer Metastasis: Roles, Mechanisms, and Applications

Dang, Qin; Shao, Bo; Zhou, Quanbo; Chen, Chen; Guo, Yaxin; Wang, Guixian; Wang, Zhibin; Kan, Quancheng; Yuan, Weitang; Sun, Zhenqiang

doi:10.3389/fonc.2021.681781

Cited by 12 publications

(11 citation statements)

References 161 publications

(342 reference statements)

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“…Considering that the methylation modifications could alter the biological function of RNA molecules at the epigenetic stage, we performed a global methylation overview of CRC ( 48 , 49 ). With the help of the MethylMix R package and Wilcox test, we found six methylation driver genes whose methylation levels were significantly negatively correlated with expression in two groups, including CES3, FAM127B, MAP9, PARVB, RLN2, and ZNF548.…”

Section: Resultsmentioning

confidence: 99%

LncRNA profiles from Notch signaling: Implications for clinical management and tumor microenvironment of colorectal cancer

et al. 2022

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The interplay between long non-coding RNAs (lncRNAs) and the Notch pathway involves a variety of malignancies. However, Notch-derived lncRNAs and their latent clinical significance remain elusive in colorectal cancer (CRC). In this study, we introduced a framework that could screen Notch-derived lncRNAs (named “NLncer”) and ultimately identified 24 NLncers. To further explore the clinical significance of these NLncers, we performed LASSO and Cox regression in TCGA-CRC cohort (n = 584) and then retained six lncRNAs tightly associated with prognosis. The final model (termed “NLncS”) was subsequently tested in GSE38832 (n = 122), GSE39582 (n = 573), and an in-house clinical cohort (n = 115). Ultimately, our NLncS model could serve as an independent risk factor and afford a robust performance for assessing the prognosis of CRC patients. Additionally, patients with high NLncS risk scores were characterized by upregulation of immune pathways, strong immunogenicity, abundant CD8 + T-cell infiltration, and potentially higher response rates to CTLA4 blockers, which turned out to be suitable for immunotherapy. Aiming at globally observing the characteristics of high-risk patients, somatic mutation and methylation modification analysis provide us with evidence at the genomic and transcriptomic levels. To facilitate the clinical transformability, we mined deeply into the sensitive compounds targeting high-risk individuals and identified dasatinib as a candidate agent for patients with a high Notch risk score. In conclusion, our NLncS model is a promising biomarker for optimizing the clinical management of CRC patients.

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Section: Resultsmentioning

confidence: 99%

LncRNA profiles from Notch signaling: Implications for clinical management and tumor microenvironment of colorectal cancer

et al. 2022

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“…Abnormal RNA modifications have been detected in a variety of diseases [ 24 , 33 , 34 ]. In particular, studies showed that RNA modification dysregulations could play important roles in cancer initiation, metastasis, prognosis, and responses to therapies [ 23 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Mechanistically, RNA modifications could affect the expression of genes involved in important oncogenic pathways such as the Wnt/β-catenin pathway, the PI3K-Akt-mTOR pathway, the JAK-STAT pathway, the MAPK pathway, the p53 pathway, the Hippo Pathway, etc.…”

Section: Epitranscriptomicsmentioning

confidence: 99%

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

Yang

Wang

2022

IJMS

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Metals are common toxic environmental pollutants. Acute or chronic exposure to metal pollutants causes severe adverse health effects in animals and humans, such as developmental retardation, abnormal metabolism, and disorders of cardiovascular, neurologic, respiratory, reproductive, and urologic systems. Moreover, several metals (arsenic, cadmium, chromium, and nickel) are classified as potent Group I carcinogens and cause various types of cancer in humans. Although the toxicity and carcinogenicity of metal pollutants are well recognized, the underlying mechanisms have not been clearly defined. The epitranscriptome includes all kinds of chemical modifications of all forms of RNA molecules inside a cell. Recent progresses in demonstrating the reversible pattern of RNA modifications and their roles in physiology and pathogenesis represent a breakthrough in the field of RNA biology and function study. The epitranscriptomic study is now an exciting emerging field in toxicology research. While few studies have been conducted so far to determine the epitranscriptomic effects of metal pollutants, they offer novel insights for understanding the mechanisms of metal toxicity and carcinogenesis. The goal of this review is to discuss recent studies on the epitranscriptomic effects of metals and propose some thoughts for future studies in the field.

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“…As m6A readers, RNA-binding proteins including YTHDF1/2/3, IGF2BP1/2/3 and HNRNPC recognize and bind to m6A sites. Among these “readers”, IGF2BP1/2/3 are mainly related to RNA stability [ 15 ]. Interestingly, IGF2BPs preferentially recognize and bind to the m6A sites of oncogene MYC in the region of the coding region instability determinant (CRD) [ 16 ], which results in enhanced MYC expression, illustrating IGF2BPs promote tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

MIR210HG promotes breast cancer progression by IGF2BP1 mediated m6A modification

et al. 2022

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Background Breast cancer is the most common cancer in women around the world, and the molecular mechanisms of breast cancer progression and metastasis are still unclear. This study aims to clarify the function and N6,2′-O-dimethyladenosine (m6A) regulation of lncRNA MIR210HG in breast cancer. Results High expression of MIR210HG was confirmed in breast cancer. MIR210HG promoted breast cancer progression, which was mediated by its encoded miR-210. MIR210HG was regulated by IGF2BP1 mediated m6A modification. IGF2BP1 was confirmed highly expressed in breast cancer and induced both MIR210HG and miR-210 expression, which contributed to breast cancer progression. In addition, MIR210HG transcript was stabilized by IGF2BP1 and co-factor ELAVL1. IGF2BP1 was a direct target of MYCN via E-box binding motif. MYCN induced IGF2BP1 expression in breast cancer cells. MIR210HG and miR-210 expressions were also increased by MYCN. Conclusions In breast cancer, MIR210HG functions as an oncogenic lncRNA, which is also mediated by its encoded miR-210. In addition, both IGF2BP1 and ELAVL1 enhance the stability of MIR210HG, which contributes to the progression of breast cancer. Interestingly, IGF2BP1 is directly activated by MYCN, which explains the oncogenic role of MYCN. These findings clarify the m6A regulation related molecular mechanism of breast cancer progression. The MYCN/IGF2BP1/MIR210HG axis may serve as an alternative molecular mechanism of breast cancer progression.

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RNA N6-Methyladenosine in Cancer Metastasis: Roles, Mechanisms, and Applications

Cited by 12 publications

References 161 publications

LncRNA profiles from Notch signaling: Implications for clinical management and tumor microenvironment of colorectal cancer

LncRNA profiles from Notch signaling: Implications for clinical management and tumor microenvironment of colorectal cancer

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

MIR210HG promotes breast cancer progression by IGF2BP1 mediated m6A modification

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