RNA bisulfite sequencing reveals NSUN2-mediated suppression of epithelial differentiation in pancreatic cancer

Chen, Szu-Ying; Chen, Kuan-Lin; Ding, Liang; Yu, Chien-Hung; Wu, Hsin‐Yi; Chou, Ya-Yi; Chang, Chia-Jung; Chang, Chih‐Han; Wu, Ya-Na; Wu, Shang Yin; Hou, Ya–Chin; Lee, Chung–Ta; Chen, Peng; Shan, Yan–Shen; Huang, Po-Hsien

doi:10.1038/s41388-022-02325-7

Cited by 33 publications

(20 citation statements)

References 42 publications

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“…As in many other types of cancers, NSUN2 regulates pancreatic tumorigenesis and epithelial differentiation through mRNA methylation ( 129 ). In contrast, NSUN6 ( 31 ) and DNMT3A ( 131 ) have inhibitory effects on pancreatic cancer and suppress the proliferation of cancerous cells, but the mechanisms remain to be elucidated.…”

Section: C Rna Modification In Cancer Cellsmentioning

confidence: 99%

Vital roles of m5C RNA modification in cancer and immune cell biology

Chen

Guan

et al. 2023

Front. Immunol.

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RNA modification plays an important role in epigenetics at the posttranscriptional level, and 5-methylcytosine (m5C) has attracted increasing attention in recent years due to the improvement in RNA m5C site detection methods. By influencing transcription, transportation and translation, m5C modification of mRNA, tRNA, rRNA, lncRNA and other RNAs has been proven to affect gene expression and metabolism and is associated with a wide range of diseases, including malignant cancers. RNA m5C modifications also substantially impact the tumor microenvironment (TME) by targeting different groups of immune cells, including B cells, T cells, macrophages, granulocytes, NK cells, dendritic cells and mast cells. Alterations in immune cell expression, infiltration and activation are highly linked to tumor malignancy and patient prognosis. This review provides a novel and holistic examination of m5C-mediated cancer development by examining the exact mechanisms underlying the oncogenicity of m5C RNA modification and summarizing the biological effects of m5C RNA modification on tumor cells as well as immune cells. Understanding methylation-related tumorigenesis can provide useful insights for the diagnosis as well as the treatment of cancer.

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Section: C Rna Modification In Cancer Cellsmentioning

confidence: 99%

Vital roles of m5C RNA modification in cancer and immune cell biology

Chen

Guan

et al. 2023

Front. Immunol.

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“…In addition, upregulated NSUN2 promotes the proliferation, migration, and invasion of BC cells [44]. NSUN2 overexpression is also associated with poor prognosis in head and neck squamous cell carcinoma [45,46], pancreatic cancer [47], bladder cancer[48],…”

Section: Underlying Mechanisms Of Nsun2 In Bc Progressionmentioning

confidence: 99%

A comprehensive investigation of crosstalk between m5C writer NSUN2 and MYC in breast cancer microenvironment

Chen

Zeng

et al. 2023

Preprint

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Background Aberrant post transcriptional modifications of RNA, such as 5-methylcytosine modifications, have been frequently observed in breast cancer (BC). The M5C core catalytic enzyme NSUN2 gene was found to be co-amplified with the oncogenic transcription factor MYC in BC. However, the function of m5C modification in the immune response and metabolism to BC remains unknown. Therefore, we aimed to investigate the crosstalk between NSUN2 and MYC in BC microenvironment. Methods We investigated the function of NSUN2 in breast cancer using vivo and vitro assays. Next, the co-occurrence of NSUN2 and MYC in BC were tested by cBioPortal analysis. Co-immunoprecipitation and mass spectrometry were performed to determine the interact between NSUN2 and MYC. Then, correlation between the expression of NSUN2 and BC microenvironment were explored by CAMOIP, PCR and western-blotting. Additionally, RNA sequencing (RNA-Seq), Gene Set Enrichment Analysis (GSEA) were used to investigate the underlying mechanism of NSUN2 in BC. Results In the current study, increased expression of NSUN2 was observed in BC tissue compared to that in the adjacent normal tissue. Elevated NSUN2 levels were associated with poor prognosis in patients with BC. NSUN2 knockout (KO) suppressed cell proliferation, migration, and invasion; induced apoptosis in vitro; and repressed tumor growth in vivo. Subsequently, we determined NSUN2 can interact with MYC protein, and found that immune infiltration and glycolysis were increased in the NSUN2 KO BC cell line. In addition, RNA sequencing demonstrated that the differentially expressed genes in BC cells after NSUN2 KO were significantly enriched in the negative regulation of immune processes and metabolic processes. Conclusions Overall, NSUN2 overexpression drove immunosuppression and promoted BC progression. NSUN2 can interact with MYC protein, thereby being involved in the functional regulation of MYC target genes. Our findings suggest that NSUN2 may act as a potential therapeutic target for BC in the context of MYC amplification.

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“…Numerous studies have revealed multiple molecular functions of m 5 C in numerous key stages of RNA metabolism, such as mRNA stability, translation, nuclear export 5,[9][10][11][12][13] . And the dynamic alterations of m 5 C play integral roles in many physiological and pathological processes, such as early embryonic development 14 , neurodevelopmental disorder 15,16 and multifarious tumorigenesis and migration [17][18][19][20] . Moreover, this modification significantly contributes to the regulation of gene expression 5,[9][10][11][12][13]17 .…”

Section: Introductionmentioning

confidence: 99%

“…And the dynamic alterations of m 5 C play integral roles in many physiological and pathological processes, such as early embryonic development 14 , neurodevelopmental disorder 15,16 and multifarious tumorigenesis and migration [17][18][19][20] . Moreover, this modification significantly contributes to the regulation of gene expression 5,[9][10][11][12][13]17 . Therefore, the detection of m 5 C sites appears to be essential for understanding its underlying effects on cellular function and disease states.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing

Zhou,

Zhao,

et al. 2024

Preprint

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5-Methylcytosine (m5C) is one of the major post-transcriptional modifications in mRNA and is highly involved in the pathogenesis of various diseases. However, the capacity of existing assays for accurately and comprehensively transcriptome-wide m5C mapping still needs improvement. Here, we develop a detection method named DRAM (deaminase and reader protein assisted RNA methylation analysis), in which deaminases (APOBEC1 and TadA-8e) are fused with m5C reader proteins (ALYREF and YBX1) to identify the m5C sites through deamination events neighboring the methylation sites. This antibody-free and bisulfite-free approach provides transcriptome-wide editing regions which are highly overlapped with the publicly available BS-seq datasets and allows for a more stable and comprehensive identification of the m5C loci. In addition, DRAM system even supports ultra-low input RNA (10ng) and monitor the dynamic accumulation of cellular m5C. We anticipate that the DRAM system could pave the way for uncovering further biological functions of m5C modifications.

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RNA bisulfite sequencing reveals NSUN2-mediated suppression of epithelial differentiation in pancreatic cancer

Cited by 33 publications

References 42 publications

Vital roles of m5C RNA modification in cancer and immune cell biology

Vital roles of m5C RNA modification in cancer and immune cell biology

A comprehensive investigation of crosstalk between m5C writer NSUN2 and MYC in breast cancer microenvironment

Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing

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