Aberrant Regulation of mRNA m6A Modification in Cancer Development

Luo, Junyun; Liu, Hui; Luan, Siyu; He, Chongsheng; Li, Zhaoyong

doi:10.3390/ijms19092515

Cited by 50 publications

(42 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Effect of m6A on cancer is reflected in the change of these tumor-related genes. Systematic study of the crosslink between substrate genes, m6A modification and post-modification regulation will contribute to reveal the mechanism of m6A in cancer comprehensively (Table 3) [116,117]. Recently, many studies choose one or two of m6A regulators to explore its aberrant expression and underlying mechanism in cancer ( Table 2).…”

Section: Roles Of M6a In Cancermentioning

confidence: 99%

Functions of N6-methyladenosine and its role in cancer

et al. 2019

Mol Cancer

927

816

View full text Add to dashboard Cite

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.

show abstract

Section: Roles Of M6a In Cancermentioning

confidence: 99%

Functions of N6-methyladenosine and its role in cancer

et al. 2019

Mol Cancer

927

816

View full text Add to dashboard Cite

show abstract

“…m6A in RNA can be removed by demethylases, termed m6A "erasers" (FTO and ALKBH5). Proteins that selectively bind m6A can be defined as m6A "readers" (HNRNPC, YTHDF1, YTHDF2, YTHDC2, and YTHDC1) that exert regulatory functions by selective recognition of methylated RNA (4). Emerging evidence has revealed the cancer promoter or suppressor role of m6A regulators in the development of various malignancies (5)(6)(7), whereas the correlation between prognosis of CESC and m6A RNA methylation regulators is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an m6A RNA Methylation Regulator-Based Signature for Prognostic Prediction in Cervical Squamous Cell Carcinoma

Pan

2020

Front. Oncol.

View full text Add to dashboard Cite

Background: Cervical squamous cell carcinoma (CESC) is one of the most common causes of cancer-related death worldwide. N6-methyladenosine (m6A) plays an important role in various cellular responses by regulating mRNA biology. This study aimed to develop and validate an m6A RNA methylation regulator-based signature for prognostic prediction in CESC. Methods: Clinical and survival data as well as RNA sequencing data of 13 m6A RNA methylation regulators were obtained from The Cancer Genome Atlas (TCGA) CESC database. Consensus clustering was performed to identify different CESC clusters based on the differential expression of the regulators. LASSO Cox regression analysis was used to generate a prognostic signature based on m6A RNA methylation regulator expression. The effect of the signature was further explored by univariate and multivariate Cox analyses. Results: Four regulators (RBM15, METTL3, FTO, and YTHDF2) were identified to be aberrantly expressed in CESC tissues. A prognostic signature that includes ZC3H13, YTHDC1, and YTHDF1 was developed, which can act as an independent prognostic indicator. Significant differences of survival rate and clinicopathological features were found between the high-and low-risk groups. The results of bioinformatics analysis were then validated in the clinical CESC cohort by qRT-PCR and immunohistochemistry staining. Conclusion: In the present study, we developed and validated an m6A RNA methylation regulator-based prognostic signature, which might provide useful insights regarding the development and prognosis of CESC.

show abstract

“…There are 3 protein classes that can regulate m 6 A modification, the 'reader' (m 6 A-binding protein), 'eraser' (m 6 A demethylating enzyme) and 'writer' (adenosine methyltransferase) (3,10,11). Specifically, m 6 A modification can be subjected to reversible installment and removal by writers and erasers, separately.…”

Section: Introductionmentioning

confidence: 99%

Profiles of m6A RNA methylation regulators for the prognosis of hepatocellular carcinoma

Chen

Huang

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

N6-methyladenosine (m 6 A) RNA methylation, which is related to cancer initiation and progression, is dynamically regulated by the m 6 A RNA methylation regulators (including 'writers', 'erasers' and 'readers'). However, the prognostic value of m 6 A RNA methylation regulators involved in hepatocellular carcinoma (HCC) carcinogenesis and progression remains to be elucidated. The aim of the present study was to determine the prognostic score in predicting the prognosis of HCC patients based on these regulators. In The Cancer Genome Atlas, most of the 13 major m 6 A RNA methylation regulators were found to be differentially expressed between HCC and normal samples (P<0.001). In addition, two subgroups (clusters 1/2) had also been identified by applying consensus clustering in the m 6 A RNA methylation regulators. As compared with the cluster 1 subgroup, the cluster 2 subgroup was correlated with a poorer prognosis, as shown by the Kaplan-Meier method (P=6.197e-4). A risk signature was constructed based on these findings using six m 6 A RNA methylation regulators, which could not only predict the clinicopathological features of HCCs, but also serve as an independent prognostic marker, as shown by Cox regression analysis (hazard ratio=1.219, 95% confidence interval: 1.143-1.299; P<0.001). Data from the International Cancer Genome Consortium were used for external validation. In addition, gene set enrichment analysis identified several pathways that m 6 A RNA methylation regulators were closely associated with. In conclusion, the m 6 A RNA methylation regulators are the crucial participants in the malignant progression of HCCs, which are potentially useful for prognosis stratification and therapeutic strategy development for HCC.

show abstract

Aberrant Regulation of mRNA m6A Modification in Cancer Development

Cited by 50 publications

References 75 publications

Functions of N6-methyladenosine and its role in cancer

Functions of N6-methyladenosine and its role in cancer

Development and Validation of an m6A RNA Methylation Regulator-Based Signature for Prognostic Prediction in Cervical Squamous Cell Carcinoma

Profiles of m6A RNA methylation regulators for the prognosis of hepatocellular carcinoma

Contact Info

Product

Resources

About