A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

Wang, Wen; Huang, Hengjun; Jiang, Hao; Tian, Chi; Tang, Yisen; Gan, Diwen; Wen, Xiaozhen; Song, Zhenyu; He, Yabai; Ou, Xijun; Fang, Liang

doi:10.3390/ijms23126584

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…However, the upstream genes that regulate NM23-H1 expression in lung cancer are not well understood [ 31 ]. Our findings suggest that over-expression of NSUN6 attenuates cell proliferation, migration, and EMT of lung cancer by regulating NM23-H1 by binding to its 3′-UTR via m5C modification, similar to other studies which have demonstrated the binding of NSUN6 to target genes through modification of m5C [ 32 ].…”

Section: Discussionsupporting

confidence: 89%

NSUN6 Regulates NM23-H1 Expression in an m5C Manner to Affect Epithelial-Mesenchymal Transition in Lung Cancer

Lu,

Liu,

Kong

et al. 2023

Med Princ Pract

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Purpose: The expression and regulatory mechanism of NSUN6 in lung cancer are still unclear. Our study explored whether NSUN6 mediates progression of lung cancer by affecting NM23-H1 expression in an m5C-dependent manner. Methods: qRT-PCR, CCK-8, colony formation, transwell and western blot analysis were employed to probe the impact of NSUN6 on lung cancer cell proliferation, migration and epithelial-mesenchymal transition (EMT). RMVar database was utilized to forecast the downstream genes of NSUN6. The mode of interaction between NSUN6 and NM23-H1 was determined by dot blot, luciferase assay, m5C RIP and cell function assays. The effect of NSUN6 expression on tumor growth was verified in vivo. Results: Expression of NSUN6 was reduced in lung cancer cells and over-expression of NSUN6 restricted the proliferation of lung cancer cells, migration and EMT. NSUN6 regulated NM23-H1 expression by modifying the 3'-UTR of NM23-H1 mRNA through m5C, and inhibited lung cancer cell proliferation, migration and EMT. In vivo experiments also showed that over-expression of NSUN6 inhibited the occurrence of lung cancer. Conclusion: NSUN6 regulates NM23-H1 expression in an m5C-dependent manner to effect EMT in lung cancer. Thus, NSUN6 may considered as a potential therapeutic target for lung cancer.

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Section: Discussionsupporting

confidence: 89%

NSUN6 Regulates NM23-H1 Expression in an m5C Manner to Affect Epithelial-Mesenchymal Transition in Lung Cancer

Lu,

Liu,

Kong

et al. 2023

Med Princ Pract

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“…For instance, NSUN6 is mainly expressed in Tregs in TNBC ( 36 ), but in exhausted CD8+ T cells, proliferating T cells and myofibroblasts in CRC ( 80 ). In addition, NSUN6 is also related to the promotion of the cell cycle ( 82 ), infiltration of B cells, CD4+ T cells and CD8+ T cells ( 36 , 80 ), and formation of antibody-secreting plasma cells ( 83 ). NSUN7 methylates eRNA, a noncoding RNA associated with transcription modulation, and enhances the expression of mRNAs coding for Pfkl, Sirt5, Idh3b and Hmox2 in a peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α)-dependent manner.…”

Section: The Mechanism and Basic Biological Functions Of M ...mentioning

confidence: 99%

“…Genes associated with m 5 C RNA modifications in B cells include NSUN2, NSUN6, DNMT3A, TET1 and TET3 ( 37 , 38 , 80 ). Specifically, although NSUN6 is dispensable for germinal center (GC) B-cell formation, it plays vital roles in the formation of antibody-secreting plasma cells ( 83 ).…”

Section: C Rna Modification In Immune 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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“…NSUN5 can bind to viral RNA and enhance the RNA-sensing function of RIG-I, functioning as a cardinal receptor ( 113 ). NSUN6 is involved in plasma cell formation ( 114 ). Meanwhile, DNMT2 responds to infection and relies on the dynamic installation of m 5 C to regulate the expression of antiviral genes, facilitating an efficient response ( 115 , 116 ).…”

Section: Non-m 6 a Rna Modifications In Antiviral ...mentioning

confidence: 99%

The regulation of antiviral innate immunity through non-m6A RNA modifications

Shen,

Zhang

2023

Front. Immunol.

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The post-transcriptional RNA modifications impact the dynamic regulation of gene expression in diverse biological and physiological processes. Host RNA modifications play an indispensable role in regulating innate immune responses against virus infection in mammals. Meanwhile, the viral RNAs can be deposited with RNA modifications to interfere with the host immune responses. The N6-methyladenosine (m6A) has boosted the recent emergence of RNA epigenetics, due to its high abundance and a transcriptome-wide widespread distribution in mammalian cells, proven to impact antiviral innate immunity. However, the other types of RNA modifications are also involved in regulating antiviral responses, and the functional roles of these non-m6A RNA modifications have not been comprehensively summarized. In this Review, we conclude the regulatory roles of 2’-O-methylation (Nm), 5-methylcytidine (m5C), adenosine-inosine editing (A-to-I editing), pseudouridine (Ψ), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N6,2’-O-dimethyladenosine (m6Am), and N4-acetylcytidine (ac4C) in antiviral innate immunity. We provide a systematic introduction to the biogenesis and functions of these non-m6A RNA modifications in viral RNA, host RNA, and during virus-host interactions, emphasizing the biological functions of RNA modification regulators in antiviral responses. Furthermore, we discussed the recent research progress in the development of antiviral drugs through non-m6A RNA modifications. Collectively, this Review conveys knowledge and inspiration to researchers in multiple disciplines, highlighting the challenges and future directions in RNA epitranscriptome, immunology, and virology.

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A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

Cited by 7 publications

References 30 publications

NSUN6 Regulates NM23-H1 Expression in an m5C Manner to Affect Epithelial-Mesenchymal Transition in Lung Cancer

NSUN6 Regulates NM23-H1 Expression in an m5C Manner to Affect Epithelial-Mesenchymal Transition in Lung Cancer

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

The regulation of antiviral innate immunity through non-m6A RNA modifications

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