Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer

Sun, Guangyu; Ma, Shenfei; Zheng, Zhiwen; Wang, Xiaohua; Chen, Shuaiqi; Chang, Taihao; Liang, Zhengxin; Jiang, Yuchen; Xu, Shengxian; Liu, Ranlu

doi:10.3389/fonc.2022.965571

Cited by 15 publications

(14 citation statements)

References 35 publications

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“…Additionally, 5‐fluorouracil (5‐FU) is the first‐line treatment for colorectal cancer 61 . High NSUN2 expression lowers the sensitivity of fluorouracil in prostate cancer 62 . Further research on combinatorial effects of verteporfin and 5‐FU may help to improve therapeutic efficacy in CRC.…”

Section: Discussionmentioning

confidence: 99%

NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization

Zou,

Huang,

Yang

et al. 2024

Clinical & Translational Med

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BackgroundNOP2/Sun domain 2 (NSUN2) is one of the important RNA methyltransferases catalyzing 5‐methylcytosine (m5C) formation and participates in many critical bioprocesses. However, the roles and underlying molecular mechanisms of NSUN2‐mediated m5C modification in colorectal cancer (CRC) remain unclear.MethodsTo explore the NSUN2 expression in CRC, fresh tissue samples were collected and Nsun2 knockout mouse was constructed. In vitro and in vivo functional assays were conducted to assess the role of NSUN2. RNA array and bisulfite sequencing were used to investigate the potential targets. The mechanisms of NSUN2 function on SKIL were identified by m5C‐methylated‐RNA immunoprecipitation and RNA stability assays. Additionally, tissue microarray analysis was conducted and patient‐derived tumour xenograft mouse (PDX) models were used to define the potential therapeutic targets.ResultsNSUN2 was highly expressed in CRC and correlated with poor CRC patient survival. Moreover, silencing NSUN2 suppressed CRC tumourigenesis and progression in Nsun2 knockout mouse models. In vitro and in vivo studies suggested that NSUN2 promoted colorectal cancer cell growth. Mechanistically, SKI‐like proto‐oncogene (SKIL) is positively regulated by NSUN2, and the NSUN2‐SKIL axis is clinically relevant to CRC. NSUN2 induced m5C modification of SKIL and stabilized its mRNA, which was mediated by Y‐box binding protein 1 (YBX1). Elevated SKIL levels increased transcriptional coactivator with PDZ‐binding motif (TAZ) activation.ConclusionsOur findings highlight the importance of NSUN2 in the initiation and progression of CRC via m5C‐YBX1‐dependent stabilization of the SKIL transcript, providing a promising targeted therapeutic strategy for CRC.

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Section: Discussionmentioning

confidence: 99%

NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization

Zou,

Huang,

Yang

et al. 2024

Clinical & Translational Med

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“…Similar to m6A, m5C modifications affect tumour migration and invasion. NOP2 and NSUN2 were found to promote prostate cancer progression by affecting ubiquitin‐mediated genes associated with the p53 signalling pathway, prostate cancer proteolysis and RNA degradation 87 . Furthermore, it was found that NSUN2 could regulate the m5C modification of the oncogene FOXC2‐AS1 and make it bind to YBX1 during GC progression 88 .…”

Section: The Emerging Roles Of Rna Methylation As Critical Regulators...mentioning

confidence: 99%

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

Chen,

Liu,

Zhang

et al. 2024

Clinical & Translational Med

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RNA methylation is widespread in nature. Abnormal expression of proteins associated with RNA methylation is strongly associated with a number of human diseases including cancer. Increasing evidence suggests that targeting RNA methylation holds promise for cancer treatment. This review specifically describes several common RNA modifications, such as the relatively well‐studied N6‐methyladenosine, as well as 5‐methylcytosine and pseudouridine (Ψ). The regulatory factors involved in these modifications and their roles in RNA are also comprehensively discussed. We summarise the diverse regulatory functions of these modifications across different types of RNAs. Furthermore, we elucidate the structural characteristics of these modifications along with the development of specific inhibitors targeting them. Additionally, recent advancements in small molecule inhibitors targeting RNA modifications are presented to underscore their immense potential and clinical significance in enhancing therapeutic efficacy against cancer.Key Points In this paper, several important types of RNA modifications and their related regulatory factors are systematically summarised. Several regulatory factors related to RNA modification types were associated with cancer progression, and their relationships with cancer cell migration, invasion, drug resistance and immune environment were summarised. In this paper, the inhibitors targeting different regulators that have been proposed in recent studies are summarised in detail, which is of great significance for the development of RNA modification regulators and cancer treatment in the future.

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“…Similar to m 6 A modification, m 5 C RNA methylation is also required for the regulation of the immune microenvironment in diverse cancer types. Increasing evidence has identified multiple m 5 C RNA regulators are abnormally expressed in many cancer tissues and play important roles in modulating immune functions in cancer 474–477 . In triple‐negative BC, NSUN2 has been found to be expressed in monocytes/macrophages and NSUN6, on the other hand, is expressed in Treg cells 478 .…”

Section: Association Of Rna Methylation With Cancer Immunitymentioning

confidence: 99%

Critical roles and clinical perspectives of RNA methylation in cancer

Li,

Yao,

Liu

et al. 2024

MedComm

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RNA modification, especially RNA methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all RNA modifications. It plays a significant role in RNA metabolism, affecting RNA processing, stability, and translation, thereby modulating gene expression and cell functions essential for proliferation, survival, and metastasis. Increasing studies have revealed the disruption in RNA metabolism mediated by RNA methylation has been implicated in various aspects of cancer progression, particularly in metabolic reprogramming and immunity. This disruption of RNA methylation has profound implications for tumor growth, metastasis, and therapy response. Herein, we elucidate the fundamental characteristics of RNA methylation and their impact on RNA metabolism and gene expression. We highlight the intricate relationship between RNA methylation, cancer metabolic reprogramming, and immunity, using the well‐characterized phenomenon of cancer metabolic reprogramming as a framework to discuss RNA methylation's specific roles and mechanisms in cancer progression. Furthermore, we explore the potential of targeting RNA methylation regulators as a novel approach for cancer therapy. By underscoring the complex mechanisms by which RNA methylation contributes to cancer progression, this review provides a foundation for developing new prognostic markers and therapeutic strategies aimed at modulating RNA methylation in cancer treatment.

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Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer

Cited by 15 publications

References 35 publications

NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization

NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

Critical roles and clinical perspectives of RNA methylation in cancer

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