Comprehensive analysis of the transcriptome-wide m6A methylome in colorectal cancer by MeRIP sequencing

Zhang, Zhen; Wang, Quan; Zhang, Mengmeng; Zhang, Wei; Zhao, Long; Yang, Changjiang; Wang, Bo; Jiang, Kewei; Ye, Yingjiang; Shen, Zhanlong; Wang, Shan

doi:10.1080/15592294.2020.1805684

Cited by 54 publications

(51 citation statements)

References 36 publications

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“…There were 4,014 differentially m6A peaks, corresponding to 2,144 genes, and each gene was associated with at least one or more m6A peaks. The distribution of m6A peaks appeared in the CDS, which was also consistent with other diseases such as cancer (Zhang et al, 2020b), traumatic brain injury (Yu et al, 2020), and preeclampsia (Wang et al, 2020a). After PNI, these m6A peaks preferentially located at the start codons (19.17 vs. 17.49%), and there was a decreasing trend in the CDS (66.75 vs. 68.49%).…”

Section: Discussionsupporting

confidence: 77%

Epitranscriptomic Analysis of m6A Methylome After Peripheral Nerve Injury

Zhang

Hao

et al. 2021

Front. Genet.

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N6-methyladenosine (m6A) is one of the most plentiful internal RNA modifications, especially in eukaryotic messenger RNA (mRNA), which plays pivotal roles in the regulation of mRNA life cycle and nerve development. However, the mRNA m6A methylation pattern in peripheral nervous injury (PNI) has not been investigated. In this study, sciatic nerve samples were collected from 7 days after sciatic nerve injury (SNI) and control rats. Quantitative real-time PCR demonstrated that m6A-related methyltransferase/demethylase genes were remarkably upregulated in SNI group compared with control group. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to reveal the m6A methylation landscape. The results showed that 4,014 m6A peaks were significantly altered, including 2,144 upregulated and 1,870 downregulated m6A peaks, which were corresponded to 1,858 genes. Moreover, 919 differentially expressed genes were identified by the conjoint analysis of MeRIP-seq and RNA-seq. GO and KEGG pathway analyses were performed to determine the biological functions and signaling pathways of the m6A-modified genes. Notably, these genes were mainly related to the immune system process, cell activation, and nervous system development in GO analysis. KEGG pathway analysis revealed that these genes were involved in the cell cycle, B cell receptor signaling pathway, axon guidance pathway, and calcium signaling pathway. Furthermore, the m6A methylation and protein expression levels of autophagy-related gene (Atg7) were increased, together with the activation of autophagy. These findings shed some light on the epigenetic regulation of gene expression, which may provide a new opinion to promote functional recovery after PNI.

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Section: Discussionsupporting

confidence: 77%

Epitranscriptomic Analysis of m6A Methylome After Peripheral Nerve Injury

Zhang

Hao

et al. 2021

Front. Genet.

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“…Most studies mainly focused on the role of SPTBN2 in neurogenesis and degenerative diseases as a structural carrier for the stabilization and activation of membrane channels, receptors, and transporters (Yildiz Bolukbasi et al, 2017;Louis and Faust, 2020). In terms of cancer research, it was identified to be associated with the tumor progression and survival of colorectal cancer patients with m6A modifications (Zhang et al, 2021). Besides, it has also been reported to be a member of a novel, competing, endogenous RNA network for the prognosis of bladder cancer (Zhang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…In terms of cancer research, it was identified to be associated with the tumor progression and survival of colorectal cancer patients with m6A modifications (Zhang et al, 2021). Besides, it has also been reported to be a member of a novel, competing, endogenous RNA network for the prognosis of bladder cancer (Zhang et al, 2021). As for BCL2L1, it is an anti-apoptotic regulator of the BCL-2 family and causes momentous effects on the integrity of the mitochondria membrane, autophagy, and cell survival ( Duan et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Analysis of the Downregulation of miRNA-1827 and Its Prognostic Significance by Targeting SPTBN2 and BCL2L1 in Ovarian Cancer

Feng

Guo

et al. 2021

Front. Mol. Biosci.

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Background: Previous studies demonstrated that miRNA-1827 could repress various cancers on proliferation, angiogenesis, and metastasis. However, little attention has been paid to its role in ovarian cancer as a novel biomarker or intervention target, especially its clinical significance and underlying regulatory network.Methods: A meta-analysis of six microarrays was adopted here to determine the expression trend of miRNA-1827, and was further validated by gene expression profile data and cellular experiments. We explored the functional annotations through enrichment analysis for the differentially expressed genes targeted by miRNA-1827. Subsequently, we identified two hub genes, SPTBN2 and BCL2L1, based on interaction analysis using two online archive tools, miRWALK (it consolidates the resources of 12 miRNA-focused servers) and Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we validated their characteristics and clinical significance in ovarian cancer.Results: The comprehensive meta-analysis revealed that miRNA-1827 was markedly downregulated in clinical and cellular specimens. Transfection of the miRNA-1827 mimic could significantly inhibit cellular proliferation. Concerning its target genes, they were involved in diverse biological processes related to tumorigenesis, such as cell proliferation, migration, and the apoptosis signaling pathway. Moreover, interaction analysis proved that two hub genes, SPTBN2 and BCL2L1, were highly associated with poor prognosis in ovarian cancer.Conclusion: These integrated bioinformatic analyses indicated that miRNA-1827 was dramatically downregulated in ovarian cancer as a tumor suppressor. The upregulation of its downstream modulators, SPTBN2 and BCL2L1, was associated with an unfavorable prognosis. Thus, the present study has identified miRNA-1827 as a potential intervention target for ovarian cancer based on our bioinformatic analysis processes.

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“…At present, a large number of studies have confirmed that m6A modification plays an important role in the occurrence and development of various cancers, including gastric cancer, 11 , 85 lung cancer, 13 breast cancer, 9 liver cancer, 10 , 62 and colon cancer. 86 , 87 CRC, as the top three cancers in the world, has been studied by many scholars with regards to the mechanism of m6A modification. Zhang et al carried out methylated RNA immunoprecipitation sequencing (MeRIP-seq) on six pairs of CRC samples and normal tissues adjacent to the tumor, and found that compared with normal tissues adjacent to the tumor, CRC samples had 1343 out-of-balance m6A peaks, of which 625 were significantly up-regulated and 718 were significantly down-regulated.…”

Section: M6a Rna Methylation Modification and Colorectal Cancermentioning

confidence: 99%

“…Genes involved in m6A peak changes play a key role in regulating glucose metabolism, RNA metabolism, and cancer stem cells. 87 Liu et al used cancer genome atlas (TCGA), the gene expression omnibus (GEO), the human protein atlas (HPA) databases, and a tissue microarray (TMA) to verify the expression of m6A-related genes at mRNA and protein levels. It was found that most m6A-related genes were significantly up-regulated in tumor tissues, while METTL14, YTHDF3, and ALKBH5 were downregulated in CRC, and there was no significant difference in FTO, 88 which suggests that the abnormal expression of m6A-related genes in CRC may play an important role in its progression.…”

Section: M6a Rna Methylation Modification and Colorectal Cancermentioning

confidence: 99%

The Emerging Clinical Application of m6A RNA Modification in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Xu¹,

Huang²,

Ocansey³

et al. 2021

JIR

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Methylation, first proposed in DNAs, but later found in RNAs, serves as one of the most widespread epigenetic modifications in eukaryotes, where N6-methyladenosine (m6A) modification has been found to play an important role in a variety of cancers including colorectal cancer (CRC). Under the action of various enzymes and proteins, the regulatory role of m6A in RNAs and immune cells has also been gradually realized. This paper reviews the general biogenesis and effects of m6A, and its emerging crucial role in intestinal mucosal immunity via the regulation of RNAs and immune cells, and thus closely related to the occurrence and development of inflammatory bowel disease (IBD) and CRC. m6A-related genes and regulatory factors are expected to be potential predictive markers and therapeutic targets.

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Comprehensive analysis of the transcriptome-wide m6A methylome in colorectal cancer by MeRIP sequencing

Cited by 54 publications

References 36 publications

Epitranscriptomic Analysis of m6A Methylome After Peripheral Nerve Injury

Epitranscriptomic Analysis of m6A Methylome After Peripheral Nerve Injury

A Comprehensive Analysis of the Downregulation of miRNA-1827 and Its Prognostic Significance by Targeting SPTBN2 and BCL2L1 in Ovarian Cancer

The Emerging Clinical Application of m6A RNA Modification in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

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