Association of tRNA methyltransferase
            <i>NSUN2/IGF-II</i>
            molecular signature with ovarian cancer survival

Yang, Jie; Risch, Eric; Zhang, Meiqin; Huang, Chan; Huang, Huatian; Lu, Lingeng

doi:10.2217/fon-2017-0084

Cited by 36 publications

(27 citation statements)

References 34 publications

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“…For example, TRMT1 catalyzed the dimethylguanosine (m 2 2 G) modification at the 26 site of tRNA molecule, and deletion of TRMT1 inhibited cell proliferation, protein synthesis, and tolerance to oxidative stress 19 . Overexpression of NSUN2 was associated with higher rate of overall and disease progression-free survival in ovarian cancer patients, suggesting that NSUN2 was a cancer suppressor for ovarian cancer 20 . ELP3 and CTU1/2 were upregulated in human breast cancers and sustained metastasis 21 .…”

Section: Introductionmentioning

confidence: 97%

FTSJ1 regulates tRNA 2ʹ-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression

Yang

Gao

et al. 2020

Cell Death Dis

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Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The mechanisms underlying NSCLC tumorigenesis are incompletely understood. Transfer RNA (tRNA) modification is emerging as a novel regulatory mechanism for carcinogenesis. However, the role of tRNA modification in NSCLC remains obscure. In this study, HPLC/MS assay was used to quantify tRNA modification levels in NSCLC tissues and cells. tRNA-modifying enzyme genes were identified by comparative genomics and validated by qRT-PCR analysis. The biological functions of tRNA-modifying gene in NSCLC were investigated in vitro and in vivo. The mechanisms of tRNA-modifying gene in NSCLC were explored by RNA-seq, qRT-PCR, and rescue assays. The results showed that a total of 18 types of tRNA modifications and up to seven tRNA-modifying genes were significantly downregulated in NSCLC tumor tissues compared with that in normal tissues, with the 2ʹ-O-methyladenosine (Am) modification displaying the lowest level in tumor tissues. Loss-and gain-of-function assays revealed that the amount of Am in tRNAs was significantly associated with expression levels of FTSJ1, which was also downregulated in NSCLC tissues and cells. Upregulation of FTSJ1 inhibited proliferation, migration, and promoted apoptosis of NSCLC cells in vitro. Silencing of FTSJ1 resulted in the opposite effects. In vivo assay confirmed that overexpression of FTSJ1 significantly suppressed the growth of NSCLC cells. Mechanistically, overexpression of FTSJ1 led to a decreased expression of DRAM1. Whereas knockdown of FTSJ1 resulted in an increased expression of DRAM1. Furthermore, silencing of DRAM1 substantially augmented the antitumor effect of FTSJ1 on NSCLC cells. Our findings suggested an important mechanism of tRNA modifications in NSCLC and demonstrated novel roles of FTSJ1 as both tRNA Am modifier and tumor suppressor in NSCLC.

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Section: Introductionmentioning

confidence: 97%

FTSJ1 regulates tRNA 2ʹ-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression

Yang

Gao

et al. 2020

Cell Death Dis

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“…Using the receiver operating characteristic (ROC) curve analysis, dNLR with the highest specificity and sensitivity was selected as the cutoff value to discriminate between long and short OS. 31 , 32 Patients were divided into two groups based on the dNLR cutoff point: the low-dNLR group (dNLR < cutoff point) and the high-dNLR group (dNLR ≥ cutoff point). The relationship between dNLR and clinicopathological features was evaluated by Chi-squared and Fisher exact tests.…”

Section: Methodsmentioning

confidence: 99%

Increased derived neutrophil-to-lymphocyte ratio and Breast Imaging-Reporting and Data System classification predict poor survival in patients with non-distant metastatic HER2+ breast cancer treated with neoadjuvant chemotherapy

Li¹,

Shao²,

Bai³

et al. 2018

CMAR

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IntroductionThe prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR) in human patients with HER2+ breast cancer is not well understood. Here, we aimed to investigate the prognostic significance of dNLR in patients with HER2+ breast cancer undergoing neoadjuvant chemotherapy.MethodsA total of 310 patients with non-distant metastatic HER2+ breast cancer who had received neoadjuvant chemotherapy in our hospital from May 2006 to November 2013 were retrospectively included in this study. Kaplan–Meier curves were used to assess overall survival (OS) and disease-free survival (DFS). The Cox regression model was used to evaluate the prognostic value of dNLR and Breast Imaging-Reporting and Data System (BI-RADS) classification, as well as other clinicopathological parameters in patients with HER2+ breast cancer treated with neoadjuvant chemotherapy.ResultsWe found that dNLR prior to treatment was positively correlated with tumor size, tumor stage, lymphovascular invasion, and histological grade (P<0.05). The median OS of patients with high dNLR and low dNLR were 44.2 and 69.9, respectively (P<0.001), and the median DFS of patients with high dNLR and low dNLR were 15.3 and 22.1 months, respectively (P<0.001). Multivariate analysis showed that dNLR was an independent risk factor for OS (HR =1.726; 95% CI: 1.072–2.662; P=0.009) and DFS (HR =1.658; 95% CI: 1.125–2.426; P=0.026). Moreover, increased BI-RADS classification independently predicted short OS (HR =1.609; 95% CI: 1.216–2.351; P=0.015) and DFS (HR =1.925; 95% CI: 1.526–2.635; P=0.021).ConclusiondNLR prior to treatment and BI-RADS classification are independent prognostic factors in patients with HER2+ breast cancer receiving neoadjuvant chemotherapy.

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“…As a target of proto-oncogene c-Myc [120], NSUN2 has been shown to play pivotal roles in many neoplasms, such as breast cancer [121], colorectal cancer [122], ovarian cancer [123], head and neck squamous carcinoma [124] as well as esophageal squamous cell carcinoma [125]. In GBM, there is no direct evidences about the biological function of NSUN2.…”

Section: Rna M 5 C Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

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Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2′O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.

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Association of tRNA methyltransferase NSUN2/IGF-II molecular signature with ovarian cancer survival

Abstract: The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

Cited by 36 publications

References 34 publications

FTSJ1 regulates tRNA 2ʹ-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression

FTSJ1 regulates tRNA 2ʹ-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression

Increased derived neutrophil-to-lymphocyte ratio and Breast Imaging-Reporting and Data System classification predict poor survival in patients with non-distant metastatic HER2+ breast cancer treated with neoadjuvant chemotherapy

The Emerging Roles of RNA Modifications in Glioblastoma

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