Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression

Xiao, Yufeng; Li, Jianmei; Wang, Sumin; Xin, Yong; Tang, Bo; Jie, Meng-Meng; Dong, Hui; Yang, Xiaochao; Yang, Shi‐Ming

doi:10.2147/ijn.s103648

Cited by 45 publications

(9 citation statements)

References 34 publications

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“…The exact mechanism by which elevated levels of DHX15 mRNAs might result in poor patient survival is currently unknown. However, a previous study on cerium oxide nanoparticles (CNPs) provides a potential link between DHX15 and poor patient survival [ 58 ]. CNPs can interfere with cancer development by inducing both cytotoxicity and oxidative stress in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…CNPs can interfere with cancer development by inducing both cytotoxicity and oxidative stress in cancer cells. The authors of the study demonstrated that treatment of gastric cells with CNPs resulted in an increased expression of DHX15 [ 58 ]. This increased expression of DHX15 was shown to activate p38 MAPK signal pathway, leading to the inhibition of proliferation and metastasis in GC both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…This increased expression of DHX15 was shown to activate p38 MAPK signal pathway, leading to the inhibition of proliferation and metastasis in GC both in vitro and in vivo . It was suggested that CNPs may be a promising approach to suppress malignant activity of GC by increasing the expression of DHX15 [ 58 ]. Clinical validation of potential tumor markers such as DHX15 will clearly continue to be a major focus of GC research in the next few years.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

et al. 2017

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Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein–Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

et al. 2017

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“…Cerium-based NPs have been successfully used in the treatment of various cancers in vivo and in vitro (Pešić et al, 2015 ; Baskar et al, 2018 ; Adebayo et al, 2020 ). Studies have shown that cerium oxide NPs can improve wound healing, reduce nerve cell death, and inhibit the growth of tumor cells by increasing ROS levels (Hijaz et al, 2016 ; Xiao et al, 2016 ; Naz et al, 2017 ). The unique redox surface chemical properties of cerium oxide NPs give them the ability to promote both antioxidation and oxidation, which, combined with low toxicity in wild-type cells, opens the possibility for a wide range of clinical applications (Wason et al, 2013 ; Rzigalinski et al, 2017 ).…”

Section: Metal-based Nanoparticles For Cancer Therapymentioning

confidence: 99%

Reactive Oxygen Species-Based Nanomaterials for Cancer Therapy

Yang

Sun

2021

Front. Chem.

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Nanotechnology advances in cancer therapy applications have led to the development of nanomaterials that generate cytotoxic reactive oxygen species (ROS) specifically in tumor cells. ROS act as a double-edged sword, as they can promote tumorigenesis and proliferation but also trigger cell death by enhancing intracellular oxidative stress. Various nanomaterials function by increasing ROS production in tumor cells and thereby disturbing their redox balance, leading to lipid peroxidation, and oxidative damage of DNA and proteins. In this review, we outline these mechanisms, summarize recent progress in ROS-based nanomaterials, including metal-based nanoparticles, organic nanomaterials, and chemotherapy drug-loaded nanoplatforms, and highlight their biomedical applications in cancer therapy as drug delivery systems (DDSs) or in combination with chemodynamic therapy (CDT), photodynamic therapy (PDT), or sonodynamic therapy (SDT). Finally, we discuss the advantages and limitations of current ROS-mediated nanomaterials used in cancer therapy and speculate on the future progress of this nanotechnology for oncological applications.

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“…This suggests that either CNPs antioxidant action is “better” than the enzymatic one, or that they may exert additional, non-redox effects. For instance, ( 39 ) showed that CNPs inhibited the migration and proliferation of gastric cancer cells by transactivating the box helicase 15 (DHX15) and its downstream MAPK signal pathway without affecting ROS levels. Therefore, when the role of CNPs in tumor microenvironment are mechanistically investigated, non-redox effects begin to emerge.…”

Section: Cnps As Anticancer Therapeutic Agentsmentioning

confidence: 99%

Not Only Redox: The Multifaceted Activity of Cerium Oxide Nanoparticles in Cancer Prevention and Therapy

et al. 2018

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Much information is accumulating on the effect of cerium oxide nanoparticles (CNPs) as cell-protective agents, reducing oxidative stress through their unique ability of scavenging noxious reactive oxygen species via an energy-free, auto-regenerative redox cycle, where superoxides and peroxides are sequentially reduced exploiting the double valence (Ce3+/Ce4+) on nanoparticle surface. In vitro and in vivo studies consistently report that CNPs are responsible for attenuating and preventing almost any oxidative damage and pathology. Particularly, CNPs were found to exert strong anticancer activities, helping correcting the aberrant homeostasis of cancer microenvironment, normalizing stroma-epithelial communication, contrasting angiogenesis, and strengthening the immune response, leading to reduction of tumor mass in vivo. Since these homeostatic alterations are of an oxidative nature, their relief is generally attributed to CNPs redox activity. Other studies however reported that CNPs exert selective cytotoxic activity against cancer cells and sensitize cancer cells to chemotherapy- and radiotherapy-induced apoptosis: such effects are hardly the result of antioxidant activity, suggesting that CNPs exert such important anticancer effects through additional, non-redox mechanisms. Indeed, using Sm-doped CNPs devoid of redox activity, we could recently demonstrate that the radio-sensitizing effect of CNPs on human keratinocytes is independent from the redox switch. Mechanisms involving particle dissolution with release of toxic Ce4+ atoms, or differential inhibition of the catalase vs. SOD-mimetic activity with accumulation of H2O2 have been proposed, explaining such intriguing findings only partially. Much effort is urgently required to address the unconventional mechanisms of the non-redox bioactivity of CNPs, which may provide unexpected medicinal tools against cancer.

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Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression

Cited by 45 publications

References 34 publications

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

Reactive Oxygen Species-Based Nanomaterials for Cancer Therapy

Not Only Redox: The Multifaceted Activity of Cerium Oxide Nanoparticles in Cancer Prevention and Therapy

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