Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer

Guan, Kelei; Liu, Xin; Li, Jianhao; Ding, Yi; Li, Juan; Cui, Guangying; Cui, Xichun; Sun, Ranran

doi:10.7150/jca.40866

Cited by 75 publications

(63 citation statements)

References 45 publications

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“…For example, as an "eraser" in the process of m 6 A RNA methylation, FTO is highly expressed in breast, liver, and gastric cancer tissues compared to normal tissues, and is associated with poor prognosis, while FTO expression in bladder cancer tissues is lower than that in normal tissues. (31)(32)(33)(34) Interestingly, in this study, we analyzed the data of 479 LUAD patients extracted from the TCGA database and showed that the 19 m 6 A RNA methylation regulators we studied had abnormal expression in LUAD patients. Among them, the expression of FTO in cancer tissues of LUAD patients is signi cantly lower than that in normal tissues, which further validates the above viewpoint.…”

Section: Discussionmentioning

confidence: 96%

Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

Wang

Feng

et al. 2020

Preprint

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Background: N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. However, data on the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) are still lacking. This paper mainly discusses the role of m6A RNA methylation regulators in LUAD, to identify novel prognostic biomarkers.Methods: The gene expression data of 19 m6A methylation regulator in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm were performed to construct a risk signature and evaluated its prognostic prediction efficiency by using the receiver operating characteristic (ROC) curve. The risk score of each patient was calculated according to the risk signature, and LUAD patients were divided into high-risk group and low-risk group. Kaplan-Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of risk signature. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the differential signaling pathways and cellular processes between the two groups.Results: The expression of 15 m6A RNA methylation regulators in LUAD tissues was significantly different than that in normal tissues. YTHDF3, YTHDF2, KIAA1429, HNRNPA2B1, RBM15, METTL3, HNRNPC, YTHDF1, IGF2BP2, IGF2BP3, IGF2BP1 were significantly up-regulated in LUAD, and the expressions of FTO, ZC3H13, WTAP, and METL14 were significantly down-regulated. We selected IGF2BP1, HNRNPC, and HNRNPA2B1 to construct the risk signature. ROC curve indicated the area under the curve (AUC) was 0.659, which means the risk signature had a good prediction efficiency. The results of Kaplan-Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD.Conclusions: The m6A RNA methylation regulators IGF2BP1, HNRNPC, and HNRNPA2B1 have a significant correlation with the clinicopathological characteristics of LUAD, which may be a promising prognostic feature and clinical treatment target.

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Section: Discussionmentioning

confidence: 96%

Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

Wang

Feng

et al. 2020

Preprint

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“…As reported recently, m6A RNA methylation is not “good or bad” in the study of m6A and tumors, because it can promote or suppress cancer cells mainly by regulating the mRNA expression of related oncogenes or tumor suppressor genes [ 25 ]. The dysregulation of m6A regulators can affect cell proliferation, cell self-renewal and differentiation capacity, control of heat shock response [ 31 ], DNA damage response [ 32 ], tissue development [ 33 ], cell death, and development of multiple forms of human diseases, including cancer [ 8 , 11 , 19 , 34 , 35 ]. Emerging evidence has demonstrated that m6A RNA methylation regulators are also involved in the occurrence and development of many cancers: hepatocellular carcinoma [ 36 , 37 ], glioblastoma [ 35 ], osteosarcoma [ 38 ], colorectal cancer [ 39 ], and so on [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…The m6A RNA methylation site in the nucleus can also be erased under the action of demethylases, known as “erasers,” mainly including ALKBH5 and FTO that can specifically target m6A RNA [ 8 , 13 – 15 ]. Subsequently, in the further processing of RNA in the nucleus and outside the nucleus, the m6A binding proteins, also known as “readers,” mainly including HNRNPC, YTHDC1, YTHDC2, YTHDF1, and YTHDF2, will bind to the m6A methylated site to perform a series of biological functions in regulating the stability, localization, transportation, translation, and degradation of target mRNAs that depended on the recognition of different kinds of “readers” [ 6 , 8 , 9 , 13 , 16 – 19 ]. Therefore, the methylation level of m6A and the expression level of m6A RNA methylation regulators may have important roles in the pathogenesis and clinical management of pRCC.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Two-m6A RNA Methylation Regulator Risk Signature as an Independent Prognostic Biomarker in Papillary Renal Cell Carcinoma by Bioinformatic Analysis

Yang

Zhao

et al. 2021

BioMed Research International

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N6-Methyladenosine (m6A), the most common form of mRNA modification, is dynamically regulated by the m6A RNA methylation regulators, which play an important role in regulating the gene expression and phenotype in both health and disease. However, the role of m6A in papillary renal cell carcinoma (pRCC) is unknown. The purpose of this work is to investigate the prognostic value of m6A RNA methylation regulators in pRCC; thus, we can build a risk score model based on m6A RNA methylation regulators as a risk signature for predicting the prognosis of pRCC. Here, we investigated the expression and corresponding clinical data by bioinformatic analysis based on 289 pRCC tissues and 32 normal kidney tissues obtained from TCGA database. As a result, we identified the landscape of m6A RNA methylation regulators in pRCC. We grouped all pRCC patients into two clusters by consensus clustering to m6A RNA methylation regulators, but we found that the clusters were not correlated to the prognosis and clinicopathological features of pRCC. Therefore, we additionally built a two-m6A RNA methylation regulator risk score model as a risk signature by the univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. The risk signature was constructed as follows: 0.031 HNRNPC + 0.199 KIAA 1429 . It revealed that the risk score was associated with the clinicopathological features such as pT status and pN status of pRCC. More importantly, the risk score was an independent prognostic marker for pRCC patients. Thus, m6A RNA methylation regulators contributed to the malignant progression of pRCC influencing its prognosis.

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“…m 6 A modification stabilises LNCAROD, and LNCAROD expression correlates with poor prognosis and tumorigenicity in HNSCC [ 128 ]. In gastric cancer, m 6 A-associated genes were found to be dysregulated, and poor prognosis correlated with high expression of FTO and WTAP [ 129 ]. Moreover, m 6 A can modulate translation in acute myeloid leukemia [ 130 ], and in response to heat shock [ 131 ].…”

Section: Looking Ahead: Rna Modifications and The Ddr A Role For Rnamentioning

confidence: 99%

Jack of all trades? The versatility of RNA in DNA double-strand break repair

Ketley

Gullerová

2020

Essays in Biochemistry

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Abstract The mechanisms by which RNA acts in the DNA damage response (DDR), specifically in the repair of DNA double-strand breaks (DSBs), are emerging as multifaceted and complex. Different RNA species, including but not limited to; microRNA (miRNA), long non-coding RNA (lncRNA), RNA:DNA hybrid structures, the recently identified damage-induced lncRNA (dilncRNA), damage-responsive transcripts (DARTs), and DNA damage-dependent small RNAs (DDRNAs), have been shown to play integral roles in the DSB response. The diverse properties of these RNAs, such as sequence, structure, and binding partners, enable them to fulfil a variety of functions in different cellular contexts. Additionally, RNA can be modified post-transcriptionally, a process which is regulated in response to cellular stressors such as DNA damage. Many of these mechanisms are not yet understood and the literature contradictory, reflecting the complexity and expansive nature of the roles of RNA in the DDR. However, it is clear that RNA is pivotal in ensuring the maintenance of genome integrity. In this review, we will discuss and summarise recent evidence which highlights the roles of these various RNAs in preserving genomic integrity, with a particular focus on the emerging role of RNA in the DSB repair response.

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Expression Status And Prognostic Value Of M6A-associated Genes in Gastric Cancer

Cited by 75 publications

References 45 publications

Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

Identification of a Two-m6A RNA Methylation Regulator Risk Signature as an Independent Prognostic Biomarker in Papillary Renal Cell Carcinoma by Bioinformatic Analysis

Jack of all trades? The versatility of RNA in DNA double-strand break repair

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