Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues

Zhang, Qiyao; Zheng, Qingyuan; Yu, Xiao; He, Yuting; Guo, Wenzhi

doi:10.1186/s12967-020-02417-6

Cited by 46 publications

(41 citation statements)

References 61 publications

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“…Recently, the regulatory role of RNA m 5 C on HCC progression has been uncovered, and evidence has indicated that the elevated m 5 C regulators NSUN4 and ALYREF are negatively correlated with poor survival outcome in HCC patients and exhibit great value as significant diagnostic and prognostic biomarkers for HCC [24]. Using 6 pairs of HCC tissues and adjacent nontumor tissues, the same study group demonstrated that the number of mRNA m 5 C peaks in HCC tissues was significantly higher than that in adjacent tissues, with a more widespread distribution [81]. Together with the bioinformatics analysis results, the study group indicated that the alteration of m5C mRNA is correlated with the pathogenesis of HCC.…”

Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

Xue

Zhao

2020

Biomark Res

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As an important posttranscriptional modification of RNA, 5-methylcytosine (m5C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m5C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m5C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m5C-based investigations. In this review, we summarize currently available approaches for detecting m5C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m5C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m5C regulators. The functional consequences of m5C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m5C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.

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Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

Xue

Zhao

2020

Biomark Res

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“…This technology basically involves the use of an antibody specific to the modification being examined and involves immunoprecipitation followed by sequencing. meRIP-Seq has been used successfully to study m5C in Arabidopsis [ 17 ] and in bacteria, archaea, and yeast [ 2 , 18 ] and, most recently, has been utilized in the study of m5C associated with mRNA in matched normal-tumor hepatocellular carcinoma (HCC) samples [ 19 ]. Two other technologies have been developed which allow research to examine for changes in m5C (or other methylation marks) that involve mechanism-based enrichment procedures specific to individual RNA methyltransferases (RNMT).…”

Section: Introductionmentioning

confidence: 99%

The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

Chellamuthu

Gray

2020

Cells

126

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5-methylcytosine is often associated as an epigenetic modifier in DNA. However, it is also found increasingly in a plethora of RNA species, predominantly transfer RNAs, but increasingly found in cytoplasmic and mitochondrial ribosomal RNAs, enhancer RNAs, and a number of long noncoding RNAs. Moreover, this modification can also be found in messenger RNAs and has led to an increasing appreciation that RNA methylation can functionally regulate gene expression and cellular activities. In mammalian cells, the addition of m5C to RNA cytosines is carried out by enzymes of the NOL1/NOP2/SUN domain (NSUN) family as well as the DNA methyltransferase homologue DNMT2. In this regard, NSUN2 is a critical RNA methyltransferase for adding m5C to mRNA. In this review, using non-small cell lung cancer and other cancers as primary examples, we discuss the recent developments in the known functions of this RNA methyltransferase and its potential critical role in cancer.

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“…Accumulating evidence indicates that the m 5 C modification status of RNA is associated with the pathogenesis of numerous types of cancers (6)(7)(8)(9), and the aberrant regulation of m 5 C changes contributes to the pathogenesis of both tumor and non-tumor diseases (8,10). Studies have also shown that m 5 Crelated regulators play essential roles in tumor progression in HCC (11,12). Research into m 5 C modifications has also provided evidence for the epigenetic m 5 C regulation of lncRNA related to HCC tumorigenesis and progression (13).…”

Section: Introductionmentioning

confidence: 99%

Multi-Omic Analyses of the m5C Regulator ALYREF Reveal Its Essential Roles in Hepatocellular Carcinoma

Xue

Zhao

et al. 2021

Front. Oncol.

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The ALYREF protein acts as a crucial epigenetic regulator in several cancers. However, the specific expression levels and functional roles of ALYREF in cancers are largely unknown, including for hepatocellular carcinoma (HCC). In a pan-cancer tissue analysis that included HCC, we assessed the expression of ALYREF compared to normal tissues using The Cancer Genome Atlas database. Associations between ALYREF gene expression and the clinical characteristics of HCC patient samples were assessed using the UALCAN database. Kaplan-Meier plots were performed to assess HCC patient prognosis, and the TIMER database was used to explore associations between ALYREF expression and immune-cell infiltrations. The same methods were used to assess eIF4A3 expression in HCC patient samples. In addition, ALYREF- and elF4A3-related differentially expressed genes (DEGs) were determined using LinkedOmics, associated protein functionalities were predicted for positively associated DEGs, and both the TargetScan and miRDB databases were used to predict potential upstream miRNAs for control of ALYREF and eIF4A3 expression. We found that ALYREF gene expression was dysregulated in several cancers and was significantly elevated in HCC patient tissue samples and HCC cell lines. The overexpression of ALYREF was significantly related to both advanced tumor-node-metastasis stages and poor HCC prognosis. Furthermore, we found that eIF4A3 expression was significantly correlated with ALYREF expression, and that upregulated eIF4A3 was significantly associated with poor HCC patient outcomes. In the protein-protein interaction network, we identified eight hub genes based on the positively associated DEGs in common between ALYREF and eIF4A3, and the high expression levels of these hub genes were positively associated with patient clinical outcomes. In addition, we identified miR-4666a-5p and miR-6124 as potential regulators of ALYREF and eIF4A3 expression. These findings suggest that increased ALYREF expression may function as a novel biomarker for both HCC diagnosis and prognosis predictions.

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Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues

Cited by 46 publications

References 61 publications

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

Multi-Omic Analyses of the m5C Regulator ALYREF Reveal Its Essential Roles in Hepatocellular Carcinoma

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