The high expression of MTH1 and NUDT5 promotes tumor metastasis and indicates a poor prognosis in patients with non-small-cell lung cancer

Li, Danni; Yang, Chengcheng; Jin, Li; Yang, Qiu-Geng Ou; Zeng, Lv-Tao; Fan, Guoqing; Liu, Tenghui; Tian, Xin-Yuan; Wang, Jingjing; Zhang, He; Dai, Da‐Peng; Chen, Ju; Cai, Jian‐Ping

doi:10.1016/j.bbamcr.2020.118895

Cited by 16 publications

(13 citation statements)

References 47 publications

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“…In addition to NUDT1, NUDT5 is also capable of degrading oxidized DNA precursors, avoiding the occurrence of mutations ( Ishibashi et al, 2003 ). Elevated NUDT5 level has been reported as a poor prognostic marker of breast cancer ( Tong et al, 2021 ), non-small cell lung cancer ( Li et al, 2021 ), esophageal squamous cell carcinoma ( Wang et al, 2020 ), and clear cell renal cell carcinoma ( Wang et al, 2017 ). NUDT11 might associate with encephalitozoonosis ( Desoubeaux et al, 2017 ), prostate cancer ( Grisanzio et al, 2012 ), and ovarian cancer ( Fortner et al, 2017 ; Katchman et al, 2017 ; Kaaks et al, 2018 )…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

Wang

Zhang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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Glioma is the most common type of central nervous system tumor with increasing incidence. 7-methylguanosine (m7G) is one of the diverse RNA modifications that is known to regulate RNA metabolism and its dysregulation was associated with various cancers. However, the expression pattern of m7G regulators and their roles in regulating tumor immune microenvironments (TIMEs) as well as alternative splicing events (ASEs) in glioma has not been reported. In this study, we showed that m7G regulators displayed a close correlation with each other and most of them were differentially expressed between normal and glioma tissues. Two m7G signatures were then constructed to predict the overall survival of both GBM and LGG patients with moderate predictive performance. The risk score calculated from the regression coefficient and expression level of signature genes was proved to be an independent prognostic factor for patients with LGG, thus, a nomogram was established on the risk score and other independent clinical parameters to predict the survival probability of LGG patients. We also investigated the correlation of m7G signatures with TIMEs in terms of immune scores, expression levels of HLA and immune checkpoint genes, immune cell composition, and immune-related functions. While exploring the correlation between signature genes and the ASEs in glioma, we found that EIF4E1B was a key regulator and might play dual roles depending on glioma grade. By incorporating spatial transcriptomic data, we found a cluster of cells featured by high expression of PTN exhibited the highest m7G score and may communicate with adjacent cancer cells via SPP1 and PTN signaling pathways. In conclusion, our work brought novel insights into the roles of m7G modification in TIMEs and ASEs in glioma, suggesting that evaluation of m7G in glioma could predict prognosis. Moreover, our data suggested that blocking SPP1 and PTN pathways might be a strategy for combating glioma.

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Section: Discussionmentioning

confidence: 99%

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

Wang

Zhang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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“…Those mentioned above in silico study, followed by the fluorescence binding study and inhibition study, clearly established the efficient binding and significant inhibition of MTH1 by compound RV. Given the reported overexpression of MTH1 in various cancers [10][11][12][13][14][15][16][17][22][23][24][25][26][27][28][29][30][31][32][33], the inhibitory potential of RV on cancer cell progression was studied. All the cell-based studies were conducted on the MCF 7 cell line, as the overexpression of MTH1 is widely reported in breast cancer [18][19][20]55].…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

“…The MTH1 protein functions to eliminate these mutagenic substrates from the precursor DNA pool, permitting the proliferation of cancer cells. Multiple studies have highlighted the sustenance of elevated MTH1 levels in various cancers, including lung cancer [11][12][13], brain tumour [14][15][16][17], breast [18][19][20][21], gastric [11,22,23], colorectal cancers [10,24], psoriasis [25,26], pancreatic ductal [11,27,28], oesophageal squamous cell carcinomas [29,30], and multiple myeloma [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy

Taiyab,

Haider,

Choudhury

et al. 2024

Preprint

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The increased metabolic activity in cancer cells often leads to higher levels of reactive oxygen species (ROS) compared to normal cells, which can cause damage to cellular components, including DNA. Cancer cells rely on MTH1 to maintain their DNA integrity and cellular function to counteract this damage. MTH1 is critical in sanitizing oxidized nucleotide pools by removing damaged nucleotides. Inhibition of MTH1 disrupts this repair process, leading to increased DNA damage and cell death in cancer cells. In this study, we present resveratrol (RV) as a potential MTH1 inhibitor. Docking and MD Simulations illustrated the effective binding of RV to the active site of the MTH1 protein, forming a notably stable complex. The fluorescence binding studies estimated a high binding affinity of RV with MTH1 (Ka − 6.2 x 105), inhibiting MTH1 activity with IC50 20.4µM. The inhibitory effects of RV on the proliferation of breast cancer cells revealed significant inhibition in cell growth, leading to apoptosis. RV significantly increases ROS production, inducing considerable oxidative stress and ultimately resulting in cell death. Our study offers a rationale for evaluating RV as an MTH1 inhibitor for potential anti-cancer therapy, particularly in breast cancer.

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“…increasing attention in cancer treatment, due to its key role in DNA repair [21]. High expression of MTH1 is deemed to be a sign for the metastasis of NSCLC [22].…”

Section: Effect Of Erl Combined With Tc-ht On Egfr Signalling Pathway...mentioning

confidence: 99%

“…In the same vein, MutT homolog 1 (MTH1) protein has received increasing attention in cancer treatment, due to its key role in DNA repair [22]. High expression of MTH1 is deemed to be a sign for the metastasis of NSCLC [23]. Therefore, the study examined MTH1 protein expression via Western blot analysis.…”

Section: Effect Of Erl Combined With Tc-ht On Egfr Signaling Pathways...mentioning

confidence: 99%

Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib

Chen

Lin

Liu

et al. 2022

Preprint

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Molecular-targeted therapy has emerged as a mainstream treatment for non-small cell lung cancer (NSCLC), the most common lung cancer, which has been the leading cause of cancer death for both men and women. Erlotinib (Erl), a targeted therapy drug which triggers epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, it has achieved only limited treatment effect, due to intrinsic and acquired resistance among most NSCLC patients. Therefore, chemosensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effect of Erl, and proved that it can sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. In addition, we found that TC-HT not only greatly enhanced the anticancer effect of Erl but also remarkably reduced the half-maximal inhibitory concentration (IC50) to as little as 0.5 μM. Besides, via regulation of thermal dosage, TC-HT alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.

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The high expression of MTH1 and NUDT5 promotes tumor metastasis and indicates a poor prognosis in patients with non-small-cell lung cancer

Cited by 16 publications

References 47 publications

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

Repurposing Resveratrol: A Novel Approach to Inhibit MTH1 for Effective Breast Cancer Therapy

Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib

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