The role of M6A modification in the regulation of tumor-related lncRNAs

Lan, Yufei; Liu, Boyang

doi:10.1016/j.omtn.2021.04.002

Cited by 52 publications

(40 citation statements)

References 150 publications

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“…Recently, various studies have identified a lot of differently expressed lncRNAs in BC and have been reported to be crucial orchestrators in the multistep process of BC tumorigenesis and malignant transformation. The m6A modification and lncRNA may play synergetic roles in tumorigenesis and development through a variety of regulatory mechanisms (9,12,14,15). For example, the m6A mediated by METTL3 was found to conduce to increase the expression of LINC00958, thereby aggravating the malignant phenotype of hepatocellular carcinoma (16).…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of m6A-Related lncRNA Signature as Potential Predictive Biomarkers in Breast Cancer

Wang

Zhao

et al. 2021

Front. Oncol.

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The metastasis and poor prognosis are still regarded as the main challenge in the clinical treatment of breast cancer (BC). Both N6-methyladenosine (m6A) modification and lncRNAs play vital roles in the carcinogenesis and evolvement of BC. Considering the unknown association of m6A and lncRNAs in BC, this study therefore aims to discern m6A-related lncRNAs and explore their prognostic value in BC patients. Firstly, a total of 6 m6A-related lncRNAs were screened from TCGA database and accordingly constructed a prognostic-predicting model. The BC patients were then divided into high-risk and low-risk groups dependent on the median cutoff of risk score based on this model. Then, the predictive value of this model was validated by the analyses of cox regression, Kaplan-Meier curve, ROC curve, and the biological differences in the two groups were validated by PCA, KEGG, GSEA, immune status as well as in vitro assay. Finally, we accordingly constructed a risk prognostic model based on the 6 identified m6A-related lncRNAs, including Z68871.1, AL122010.1, OTUD6B-AS1, AC090948.3, AL138724.1, EGOT. Interestingly, the BC patients were divided into the low-risk and high-risk groups with different prognoses according to the risk score. Notably, the risk score of the model was an excellent independent prognostic factor. In the clinical sample validation, m6A regulatory proteins were differentially expressed in patients with different risks, and the markers of tumor-associated macrophages and m6A regulators were co-localized in high-risk BC tissues. This well-validated risk assessment tool based on the repertoire of these m6A-related genes and m6A-related lncRNAs, is of highly prognosis-predicting ability, and might provide a supplemental screening method for precisely judging BC prognosis.

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Section: Introductionmentioning

confidence: 99%

Identification and Validation of m6A-Related lncRNA Signature as Potential Predictive Biomarkers in Breast Cancer

Wang

Zhao

et al. 2021

Front. Oncol.

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“…LncRNAs are a class of non-coding RNAs greater than 200 nucleotides in length with limited or no protein-coding capacity that possess complex spatial structures and diverse functions ( Chen and Carmichael, 2010 ; Xie et al, 2021a ). Numerous studies have shown that lncRNAs play a significant role in biological functions, such as epigenetic modification, mRNA transcription, splicing, stability and translation ( Lan et al, 2021 ). Functionally, lncRNAs can either act in cis by regulating the expression of neighboring genes or in trans by regulating the expression of distant genes ( Ulitsky and Bartel, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…These data suggested that m 6 A modification could mediate muscle progenitor cell proliferation and differentiation. It has been demonstrated that m 6 A lncRNA modification plays roles in different biological processes ( Patil et al, 2016 ; Yang D. et al, 2018 ; Fazi and Fatica, 2019 ; Ma et al, 2019 ; He et al, 2020 ; Lan et al, 2021 ). However, little is known about the m 6 A methylation status of lncRNAs involved in developing skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Long Non-coding RNAs Modified by m6A RNA Methylation in Skeletal Myogenesis

Xie

Tao

Diao

et al. 2021

Front. Cell Dev. Biol.

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Proper development of mammalian skeletal muscle relies on precise gene expression regulation. Our previous studies revealed that muscle development is regulated by both mRNA and long non-coding RNAs (lncRNAs). Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various biological processes, making it essential to profile m6A modification on a transcriptome-wide scale in developing muscle. Patterns of m6A methylation in lncRNAs in developing muscle have not been uncovered. Here, we reveal differentially expressed lncRNAs and report temporal m6A methylation patterns in lncRNAs expressed in mouse myoblasts and myotubes by RNA-seq and methylated RNA immunoprecipitation (MeRIP) sequencing. Many lncRNAs exhibit temporal differential expression, and m6A-lncRNAs harbor the consensus m6A motif “DRACH” along lncRNA transcripts. Interestingly, we found that m6A methylation levels of lncRNAs are positively correlated with the transcript abundance of lncRNAs. Overexpression or knockdown of m6A methyltransferase METTL3 alters the expression levels of these lncRNAs. Furthermore, we highlight that the function of m6A genic lncRNAs might correlate to their nearby mRNAs. Our work reveals a fundamental expression reference of m6A-mediated epitranscriptomic modifications in lncRNAs that are temporally expressed in developing muscle.

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“…Meanwhile, there was a close correlation between lncRNAs and m6A regulators ( 24 , 29 ). Their interaction could regulate the expression of target genes as well as the cellular biological functions ( 21 , 32 , 33 ). Thus, in this study, we identified m6A-related lncRNAs to construct a risk model in LUSC.…”

Section: Discussionmentioning

confidence: 99%

“…N6-Methyladenosine (m6A), as the most abundant and reversible RNA modification, is involved in the regulation of RNA splicing, localization, stability, and translation ( 19 , 20 ). m6A modification could regulate the expression and biological processes of mRNAs and non-coding RNAs ( 21 , 22 ). The m6A-regulated process was involved in three kinds of m6A regulators, which include methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers).…”

Section: Introductionmentioning

confidence: 99%

Identification of a N6-Methyladenosine (m6A)-Related lncRNA Signature for Predicting the Prognosis and Immune Landscape of Lung Squamous Cell Carcinoma

et al. 2021

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Backgroundm6A-related lncRNAs emerged as potential targets for tumor diagnosis and treatment. This study aimed to identify m6A-regulated lncRNAs in lung squamous cell carcinoma (LUSC) patients.Materials and MethodsRNA sequencing and the clinical data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The m6A-related lncRNAs were identified by using Pearson correlation assay. Univariate and multivariate Cox regression analyses were utilized to construct a risk model. The performance of the risk model was validated using Kaplan–Meier survival analysis and receiver operating characteristics (ROC). Immune estimation of LUSC was downloaded from TIMER, and the correlations between the risk score and various immune cells infiltration were analyzed using various methods. Differences in immune functions and expression of immune checkpoint inhibitors and m6A regulators between high-risk and low-risk groups were further explored. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to explore the biological functions of AL122125.1.ResultsA total of 351 m6A-related lncRNAs were obtained from TCGA. Seven lncRNAs demonstrated prognostic values. A further multivariate Cox regression assay constructed a risk model consisting of two lncRNAs (AL122125.1 and HORMAD2-AS1). The Kaplan–Meier analysis and area under the curve indicated that this risk model could be used to predict the prognosis of LUSC patients. The m6A-related lncRNAs were immune-associated. There were significant correlations between risk score and immune cell infiltration, immune functions, and expression of immune checkpoint inhibitors. Meanwhile, there were significant differences in the expression of m6A regulators between the high- and low-risk groups. Moreover, GO and KEGG analyses revealed that the upregulated expression of AL122125.1 was tumor-related.ConclusionIn this study, we constructed an m6A-related lncRNA risk model to predict the survival of LUSC patients. This study could provide a novel insight to the prognosis and treatment of LUSC patients.

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The role of M6A modification in the regulation of tumor-related lncRNAs

Cited by 52 publications

References 150 publications

Identification and Validation of m6A-Related lncRNA Signature as Potential Predictive Biomarkers in Breast Cancer

Identification and Validation of m6A-Related lncRNA Signature as Potential Predictive Biomarkers in Breast Cancer

Characterization of Long Non-coding RNAs Modified by m6A RNA Methylation in Skeletal Myogenesis

Identification of a N6-Methyladenosine (m6A)-Related lncRNA Signature for Predicting the Prognosis and Immune Landscape of Lung Squamous Cell Carcinoma

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