N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2

Wang, Hong; Xu, Bei; Shi, Jun

doi:10.1016/j.gene.2019.144076

Cited by 159 publications

(152 citation statements)

References 20 publications

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“…To date, only one study has reported that m6A is associated with HNSCC, in which METTL3-mediated ZNF750 repression facilitates NPC progression. METTL3 can promote apoptosis in gastric (36) and breast cancer cells (37) and is associated with ubiquitin-dependent process in pancreatic cancer cells (38). These pathways are similar to those involving YTHDC2.…”

Section: Discussionmentioning

confidence: 79%

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma

et al. 2020

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Genetic alteration involving N6-methyladenosine (m6A) regulatory genes is a frequent characteristic of multiple tumors. Nevertheless, little is known regarding their genetic alteration signatures and prognostic values in head and neck squamous cell carcinoma (HNSCC). In this study, RNA sequence profiles and copy number variation (CNV) data of 506 HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Correlation analysis involving alteration of m6A regulatory genes, clinicopathological characteristics, and patient survival was performed using R language. The results suggest that alteration of m6A regulatory genes was correlated with clinical staging. Patients with high expression of ALKBH5, FTO, METTL14, WTAP, YTHDC1, YTHDF1, and YTHDF2 had poor overall survival (OS) than those with low expression. Univariate and multivariate Cox regression analyses showed that ALKBH5 and YTHDC2 were independent risk factors for OS. However, patients with high YTHDC2 expression had better OS. Moreover, according to machine learning results, YTHDC2 was found to be the most important gene among the 10 m6A regulators. Additionally, high expression of YTHDC2 was correlated with activation of apoptosis and ubiquitin-mediated proteolysis. Here, we identified alterations to m6A regulatory genes in HNSCC for the first time and found that seven m6A regulators were associated with poor prognosis, especially ALKBH5, whereas YTHDC2 was associated with better prognosis. These m6A-related regulators could act as novel prognostic biomarkers for HNSCC. Our findings provide clues for understanding RNA epigenetic modifications in HNSCC.

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Section: Discussionmentioning

confidence: 79%

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma

et al. 2020

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“…Recent studies showed that METTL3 was upregulated in breast cancer tissue and cells. Knockdown of METTL3 reduced cell proliferation and accelerated apoptosis and migration by targeting Bcl-2, suggesting the oncogenic role of METTL3 in breast cancer (41,42). However, another study that explored key m 6 A-related enzymes via combined analysis of data from the ONCOMINE and The Cancer Genome Atlas databases with 36 pairs of breast cancer and adjacent non-cancerous tissues, revealed that the expression of all m 6 A methylases, including METTL3, was reduced in breast cancer.…”

Section: Mettl3 In Breast Cancermentioning

confidence: 99%

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

et al. 2019

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Methyltransferase-like 3 (METTL3), a predominantly catalytic enzyme in the N 6 -methyladenosine (m 6 A) methyltransferase system, is dysregulated and plays a dual role (oncogene or tumor suppressor) in different human cancers. The expression and pro-or anticancer role of METTL3 in different cancers remain controversial. METTL3 is implicated in many aspects of tumor progression, including tumorigenesis, proliferation, invasion, migration, cell cycle, differentiation, and viability. Most underlying mechanisms involve multiple signaling pathways that rely on m 6 A-dependent modification. However, METTL3 can also modulate the cancer process by directly promoting the translation of oncogenes via interaction with the translation initiation machinery through recruitment of eukaryotic translation initiation factor 3 subunit h (eIF3h). In this review, we summarized the current evidence on METTL3 in diverse human malignancies and its potential as a prognostic/ therapeutic target.

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“…This modification can significantly regulate the occurrence of human cancer, which may be exploited to develop new biomarkers for detection and novel therapeutic targets for clinical studies of malignant tumors. A recent study suggested that the m 6 A level in BC tissues was increased compared with noncancerous tissues [21]. We measured the contents of m 6 A in the peripheral blood of 62 patients with BC and found that they were significantly higher than the levels in patients with BBD or the NCs.…”

Section: Combined Diagnostic Value Of M 6 a The Mettl14 Mrna Level mentioning

confidence: 77%

Upregulated N6-Methyladenosine RNA in Peripheral Blood: Potential Diagnostic Biomarker for Breast Cancer

et al. 2021

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An effective biomarker for the diagnosis of breast cancer (BC) and benign breast diseases (BBD) is crucial for improving the prognosis. We investigated whether N6-methyladenosine (m 6 A) can be a diagnostic biomarker of BC. Materials and Methods We detected the contents of peripheral blood m 6 A in 62 patients with BC, 41 patients with BBD, and 41 normal controls (NCs) using the colorimetric method. The relative expression of the m 6 A regulated genes METTL14 and FTO was analyzed using quantitative real-time polymerase chain reaction. Results m 6 A in peripheral blood RNA was significantly higher in patients with BC than that in patients with BBD (p < 0.0001) or the NCs (p < 0.0001). m 6 A was closely associated with the disease stage (from stage 0 to stage I-Ⅳ; p = 0.003). The receiver operating characteristic curve of m 6 A contained an area under the curve (AUC) value of 0.887 in BC, which was greater than that of CEA or CA153. The combination of m 6 A, CEA, and CA153 improved the AUC to 0.914. The up-and downregulated mRNA expression of METTL14 and FTO, respectively, might contribute to the increase of m 6 A in patients with BC. m 6 A combined with METTL14 and FTO improved the AUC to 0.929 with a specificity of 97.4% in the peripheral blood of patients with BC. Conclusion The peripheral blood RNA of m 6 A might be a valuable biomarker for the diagnosis of BC.

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N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2

Cited by 159 publications

References 20 publications

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

Upregulated N6-Methyladenosine RNA in Peripheral Blood: Potential Diagnostic Biomarker for Breast Cancer

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