Oxidative Medicine and Cellular Longevity

Volume 2022, Issue 1 5413035

Research Article

Open Access

Expression of eIF4E Gene in Glioma and Its Sensitivity to Oxidative Stress

Jian Liang

Department of Neurosurgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong 518020, China jnu.edu.cn

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Yaoqiang Yang,

Yaoqiang Yang

First Clinical Medical College of Jinan University, Jinan University, Guangzhou 510630, China jnu.edu.cn

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Xing Li,

Xing Li

School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China sustc.edu.cn

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Guangmou Cai,

Guangmou Cai

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Jianxuan Cao,

Jianxuan Cao

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Bo Zhang,

Corresponding Author

Bo Zhang

[email protected]

orcid.org/0000-0002-3217-1328

Department of Neurosurgery, The Shenzhen Luohu Hospital Group, The Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, China szu.edu.cn

Neurosurgery Department of School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China cuhk.edu.hk

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Jian Liang,

Jian Liang

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Yaoqiang Yang,

Yaoqiang Yang

First Clinical Medical College of Jinan University, Jinan University, Guangzhou 510630, China jnu.edu.cn

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Xing Li,

Xing Li

School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China sustc.edu.cn

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Guangmou Cai,

Guangmou Cai

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Jianxuan Cao,

Jianxuan Cao

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Bo Zhang,

Corresponding Author

Bo Zhang

[email protected]

orcid.org/0000-0002-3217-1328

Department of Neurosurgery, The Shenzhen Luohu Hospital Group, The Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, China szu.edu.cn

Neurosurgery Department of School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China cuhk.edu.hk

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First published: 03 October 2022

https://doi.org/10.1155/2022/5413035

Citations: 5

Academic Editor: Shao Liang

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Abstract

Objective. Increased expression of eIF4E has been observed in various cancers, which makes eIF4E an attractive target of anticancer drugs. This study mainly discussed eIF4E gene expression in glioma and its sensitivity to oxidative stress (OS). Methods. Relevant data from The Cancer Genome Atlas (TCGA) database regarding eIF4E gene expression and its prognostic significance in glioma samples were analyzed. Additionally, we measured eIF4E at mRNA and protein levels in clinical samples collected between July 2019 and September 2021, as well as glioma cell strains. U251 cells cultured in vitro were treated with OS injury induced by hydrogen peroxide (H₂O₂) and then transfected with si-eIF4E to determine changes in cell multiplication, invasiveness, and migration capacities as well as apoptosis rate. ELISA quantified cell malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) concentrations, and flow cytometry measured reactive oxygen species (ROS) level. Results. In glioma samples from the TCGA database, eIF4E showed obviously elevated levels in LGG and GBM patients, which was usually associated with adverse patient prognosis (P < 0.05). eIF4E was also upregulated in glioma cell strains than in HBE cells. In comparison with the blank control group, transfection of si-eIF4E statistically suppressed the capacity of U251 cells to proliferate, invade and migrate, and enhance apoptosis rate, while reducing SOD and GSH-Px and increasing MDA and ROS. In addition, H₂O₂ induced the upregulation of eIF4E in U251 cells. H₂O₂ + si-eIF4E exhibited reduced multiplication and number of clone cell formation, invasion, and migration of U251 cells, as well as increased apoptosis rate than H₂O₂ + si-NC group. Conclusions. eIF4E is highly expressed in glioma. Knocking down eIF4E can effectively inhibit the capacity of U251 to proliferate, invade and migrate, and significantly increase apoptosis. In addition, eIF4E knock-down is able to lower OS reaction under H₂O₂ inducement and enhance U251 cells’ sensitivity to OS.

1. Introduction

Glioma, an aggressive primary cerebral tumor most frequently occurring in the central nervous system, accounts for about four-fifths of primary malignant cerebral tumors and is the major inducement of death in children and adults [1, 2]. Although the molecular mechanisms underlying the occurrence of glioma have been gradually revealed over the years and innovative therapeutic strategies have been proposed, no successful clinical methodology has been found [3, 4]. Improved survival and quality of life have been realized, attributing to advances in molecular and genetic technology and the understanding of physiological and biochemical pathways of the disease [5, 6]. However, the overall survival of glioma patients is merely 12–15 months [7, 8].

The uncontrolled reactive oxygen species (ROS) production and the products produced by their interactions with biomolecules and cells have contributed to several pathological etiologies, among which cancer is the most reported one [9–11]. Oxidative stress (OS) and ROS are closely related to cancer genesis and progression. OS refers to the relative ROS excess compared to antioxidants [12]. Carcinoma cells exhibit aberrant redox homeostasis, while ROS is tumor-promoting and high-level ROS is cytotoxic [13]. To be specific, there is high ROS production during the hyperproliferation of tumor cells, but the cells get adapted to grow in a reduced state where this oxidation load pushes the redox balance away. Tumor cells optimize ROS-driven proliferation by increasing their antioxidant status while avoiding senescence, apoptosis, or ferroptosis triggered by ROS thresholds [14, 15]. Over the past few decades, antioxidant molecules have been recognized as one of the most effective alternative and complementary therapies for diseases, combining treatment with prevention [16]. Therefore, we believe that based on this, enhancing the sensitivity of cancer cells to OS may improve the therapeutic effect of OS inducers.

Translation control, which plays a vital part in regulating gene expression in eukaryotes, influences various crucial cell processes such as differentiation, multiplication, and apoptosis. In most cases, translation control takes place in the initial step of ribosome recruitment into mRNA [17]. As a part of the eIF4F complex, the eucaryotic translation initiation factor 4E (eIF4E) first establishes interactions with mRNAs to promote the 40S ribosome subunit recruitment [18]. eIF4E is essential in a wide spectrum of human tumors, including carcinomas of the breast [19], head and neck [20], urinary bladder [21], and cervix [22]. eIF4E overexpression or knockout provides clues for its functional significance in tumorigenesis. Studies have shown that knocking down eIF4E can inhibit cancer cell proliferation and angiogenesis [23, 24]. In addition, increased eIF4E can lead to drug resistance to multiple chemotherapeutic drugs. Moreover, the combined use of eIF4E-silencing chemotherapy enhanced sensitivity to chemotherapeutics (paclitaxel, cisplatin, adriamycin, docetaxel, etc.) [25–27]. Truitt et al. found that the dose of eIF4E in mice is crucial for the translation of mRNAs that regulate ROS, the promotion of in vivo transformation, and the survival of cancer cells [28]. In addition to playing a part in translation, eIF4E can also modulate gene subsets related to key stress reactions in animals, including detoxifying ROS for normal cell function and controlling OS [29].

However, there are few studies investigating eIF4E expression and revealing its potential role in glioma. Thus, the motivation and novelty of this study are to demonstrate eIF4E overexpression and clarify the biological function of eIF4E under OS in glioma cells. In addition, this study aims to explore eIF4E gene expression in glioma and its sensitivity to OS.

2. Data and Methods

2.1. Database Analysis and Clinical Tissue Samples

eIF4E mRNA levels were analyzed with 163 GBM samples, 518 LGG samples, and 207 normal counterparts retrieved from the Gene Expression Profiling Interactive Analysis 2 (GEPIA2; URL: http://gepia2.cancer-pku.cn/#index).

In addition, clinical tissue (carcinoma tissues and adjacent counterparts) samples were collected from 36 pathologically confirmed glioma patients (age: 29–71, mean: 40.7 ± 13.8) presented to our hospital between July 2019 and September 2021. All cases enrolled were treatment-naive without any preoperative radiotherapy, chemotherapy, or biological therapy, with their specimens stored in −196°C liquid nitrogen. The hospital ethics committee approved this research, and all patients signed an informed consent form authorizing the use of their tissue specimens.

2.2. Cell Culture

Ordered from Shanghai Cell Bank, Chinese Academy of Sciences, human glioma cells (U87-MG, T98G, U251, and LN229) and human brain astrocytes HEB were all immersed in Dulbecco’s modified Eagle’s medium (DMEM, Gibco, USA) + 10% fetal bovine serum (FBS, Gibco, USA) + 100 U/mL penicillin + 100 μg/mL streptomycin for routine culture in an incubator under the conditions of 37°C and 5% CO₂, except that U87-MG, T98G, U251, and HEB were grown in high-glucose DMEM, while LN229 cells in low-glucose DMEM.

2.3. Cell Transfection and Intervention

RiboBio (Guangzhou) synthesized three different ATG4C small interfering RNAs (siRNAs) and a negative control siRNA. The exponentially growing cells were inoculated in the wells of 6 well plates for overnight culture. According to the Lipofectamine RNAiMAX reagent (Invitrogen, CA, USA) instructions, the designated siRNAs with a final concentration of 50 nM were transfected into 60–70% confluent plated cells. Lipofectamine 3000 reagent (Invitrogen, CA, USA) was used to transfect cells planted in the 6-well plates with RFP-GFP-LC3B plasmids (provided by Professor Cheng from Central South University) at 1.0 μg/well following the instructions. The medium was replaced with fresh medium + 10% FBS 6 hours post intervention, and the transfected cells were collected for further analysis.

2.4. Hydrogen Peroxide (H₂O₂) Treatment

Cell damage was induced by a certain concentration of H₂O₂, and the experimental cells were assigned to 3 groups: control, H₂O₂ (1 mM H₂O₂ intervention for 24 h), and si-eIF4E + H₂O₂ (1 mM H₂O₂ intervention for 24 h after eIF4E siRNA transfection).

2.5. qRT-PCR

After extraction by TRIzol reagent (Invitrogen), the total cell RNA underwent reverse transcription into cDNA with a Prime Script RT Reagent kit (Takara) by referring to the supplier’s recommendations. Then, real-time PCR was carried out with the Stepone plus system (Applied Biosystems) as instructed by the SYBR Premix Ex Taq Kit (Takara) instructions, followed by PCR reactions using eIF4E as the primer: sense: 5′-TGCGGCTGATCTCCAAGTTTG-3′, anti-sense: 5′-CCCACATAGGCTCAATACCATC-3′; GAPDH: sense: 5′-CTGGGCTACACTGAGCACC-3′, anti-sense: 5′-AAGTGGTCGTTGAGGGCAATG-3. The internal reference was GAPDH. The 2^−ΔΔCt method was employed for the calculation of gene expression levels. All experiments were repeatedly determined three times.

2.6. Western Blot

Total cell proteins were extracted after cell lysis by RIPA. Protein concentration was determined by the BCA method, and the protein loading amount was 40 μg. The protein samples were shifted to a PVDF membrane post 12% SDS-PAGE. 5% skim milk powder was then used to seal at an ambient temperature for 1 h, and the primary antibody eIF4E (1 : 1000, Cell Signaling Technology, USA) was added to incubate at 4°C overnight. The next day, the second antihorseradish peroxidase labeled antirabbit IgG antibody (1 : 2000, Cell Signaling Technology, USA) was added correspondingly. The electrochemiluminescence (ECL) method was adopted for color development. Images were collected by gel imaging system and processed by software Image J for gray level analysis. GAPDH was used as internal reference for semiquantitative protein analysis.

2.7. CCK-8

After entering the logarithmic growth phase (LGF), the cells (2 × 10⁴/mL) were inoculated into the wells of a 96-well plate for a 24-hour culture under the conditions of 5% CO₂ and 37°C. Cells in each well were then added with CCK-8 reagent with a volume of 10 μl at 0, 12, 24, 48, and 72 h, respectively, and cultivated at indoor temperature for 2 hours, after which absorbance_450nm was determined with a multifunctional microplate reader.

2.8. Cell Clone Formation

LGF cells of each group were digested and centrifuged, and evenly inoculated into 6-well plates after adjusting to 200 cells/mL by in a medium. After putting 1 mL cell suspension to each well, the 6-well plates were placed into an incubator (5% CO₂ and 37°C) for culture with the medium changed once every 4 days. When the number of cloned cells was more than 50, the culture was terminated, the supernatant was discarded, and the PBS solution was used for cleaning. After immobilization and cleaning with methanol, cells were added with crystal violet dyeing solution for dyeing in the dark for about 20 min, after which washing and drying of cells were performed. The number of cell clones with cells greater than 50 was analyzed and counted.

2.9. Transwell for Cell Invasiveness and Migration Detection

The transfected cells cultured to LGF were gathered, digested with trypsin, centrifuged, and thoroughly mixed with blank culture medium. Cells were laid (1 × 10⁵ cells/well) on the upper Transwell chamber coated with Matrigel, while the lower chamber was pre-added with 500 μL of medium + 10% FBS. The upper chamber was then placed into a 24-well plate. After culturing in a cell incubator for 24 h, the medium was poured out, PBS-washed, air-dried, 4% paraformaldehyde-fixed, and 0.14% crystal violet-stained. The inverted microscope randomly selected five nonoverlapping fields for counting and photographing. The cell migration experiment did not need to spread Matrigel matrix glue in the upper chamber of Transwell chamber, and cell suspension was placed into the chamber for 24 h of culture. Other steps were basically the same as invasiveness detection.

2.10. OS Index Detection

Cells in each group were collected and lysed with cell lysate, and supernatant was collected to quantify SOD, MDA, and GSH-Px contents following kit manuals. Endogenous ROS fluorescence intensity was detected using the 2′,7′-dichlorofluorescein-diacetate (DCFH-DA) probe. Cells of each group (5 × 10³ cells/mL) were inoculated into the wells of a 96-well plate for 48 hours of culture, and then, the fluorescent probe DCFH-DA (10 μmol/L) was added for incubator incubation (37°C, 20 min). After washing, the mean fluorescence intensity (MFI) of cells was detected by flow cytometry (FCM), representing the intracellular ROS level. The excitation and emission wavelengths were 488 nm and 525 nm, respectively.

2.11. Apoptosis Detection

After 0.25% trypsin digestion, LGF cells were treated with 10 min of centrifugation (1000 rpm, 4°C), and three repeated rinsing. Single-cell suspension was prepared, and cells were suspended in 200 μL buffer and then incubated with 5 μL Annexin V-FITC and 10 μL PI in turn, after which FCM was performed to determine cell apoptosis.

2.12. Statistical Processing

SPSS25.0 processed the data. Mean values were obtained after three measurements of each test, and the data was denoted by the mean ± standard deviation. The Mann-Whitney U test was used to compare eIF4E expression between GBM, LGG samples, and normal samples. Comparisons between groups and among multiple groups were made by Student’s t-test and one-way ANOVA plus Tukey post hoc test, respectively. The test level was α = 0.05, and significance was determined at P < 0.05.

3. Results

3.1. Expression Profiling and Prognosis Significance of eIF4E in Glioma Patients

GEPIA2 was adopted to analyze eIF4E expression in LGG and GBM patients in the TCGA database. The results identified statistically elevated eIF4E expression in cancer tissues of LGG and GBM patients compared with normal counterparts (P < 0.05; Figure 1(a)). Consistent findings were obtained when detecting eIF4E in the obtained clinical tissue samples; namely, eIF4E was upregulated in carcinoma tissues compared with adjacent normal counterparts (P < 0.05; Figure 1(b)). Patients were grouped as high- and low-expression groups based on the median expression level. According to Kaplan-Meier survival analysis, patients with high eIF4E expression had obviously worse outcomes than those with low expression (P < 0.05; Figures 1(c) and 1(d)).

Details are in the caption following the image — Open in figure viewer PowerPoint

3.2. eIF4E Expression in Glioma Cells

qPCR and Western blot analyses revealed statistically regulated eIF4E mRNA and protein levels in glioma cell lines compared with HBE cells (P < 0.05), with the highest upregulation found in U251 cells (Figure 2).

3.3. Influence of down-Regulating eIF4E on U251 Cell Biological Function

The potential function of eIF4E in U251 cells was studied by transfecting si-eIF4E into U251 cells. Western blotting was performed to confirm that eIF4E was effectively downregulated by siRNA, and as expected, markedly reduced eIF4E protein was observed in U251 cells after si-eIF4E transfection (P < 0.05; Figure 3(a)). si-eIF4E transfection evidently prevented U251 cells from proliferating (Figure 3(b)) and reduced the number of cell clones (Figure 3(c)). Meanwhile, downregulating eIF4E validly suppressed the capacity of U251 cell to invade and migrate, and increased apoptosis (Figures 3(d) and 3(e)).

3.4. Downregulating eIF4E Enhances U251 Cells’ Sensitivity to OS

To determine the protective action of eIF4E against OS in glioma cells, we treated U251 cells with H₂O₂. Under H₂O₂-induced OS, eIF4E increased with time at both mRNA and protein levels (P < 0.05; Figures 4(a) and 4(b)). After transfecting stimulated U251 cells with si-eIF4E, it was found that compared with the H₂O₂ + si-NC group, the proliferation rate of U251 in the H₂O₂ + si-eIF4E group decreased, the number of cell clones as well as invading and migrating cells declined, and the apoptosis rate elevated (P < 0.05; Figures 4(c)–4(f)). These results suggest that downregulating eIF4E may enhance glioma cells’ sensitivity to OS.

3.5. Impact of Downregulating eIF4E on OS Indexes in U251 Cells after H₂O₂ Induction

The H₂O₂ + si-NC group exhibited statistically decreased SOD and GSH-Px and increased MDA and ROS than the U251 group (P < 0.05). Moreover, in comparison with the H₂O₂ + si-NC group, SOD and GSH-Px in U251 cells in the H₂O₂ + si-eIF4E group increased, while MDA and ROS decreased (P < 0.05; Figure 5).

4. Discussion

eIF4E activity abnormalities have been demonstrated in multiple human malignancies, and eIF4E overexpression is commonly observed in the breast, lung, stomach, colon, prostate, skin, and hematopoietic system. The elevation of eIF4E expression is related to the increase of disease grade [30–35]. However, it remains to define the correlation of eIF4E gene with glioma progression. This study is the first to demonstrate that eIF4E is overexpressed in glioma clinical samples and cells and that overexpression of eIF4E is significantly linked to adverse prognosis in such patients. Meanwhile, eIF4E knock-out prevented U251 cells from proliferating, invading, and migrating and increased the apoptosis rate. All these suggest the role of eIF4E gene as an attractive potential target for glioma therapy. Studies have shown that translation initiation depends primarily on eIF4E activity. Translational activation, as we know, is essential for carcinoma cell growth and survival, making translation a logical target for new anticancer treatments. Studies on different tumors indicated that eIF4E could be modulated at many levels by MAPK/MNK and PI3K/mTOR axis, like through serine 209 phosphorylation, transcription, and inhibitory interaction between binding proteins [36, 37]. Furthermore, elevated total eIF4E levels, together with 4EBP1 hyperphosphorylation, increased the effectiveness of eIF4E binding to eIF4G and enhanced cap-dependent translationa phenomenon found in breast and prostate carcinomas, while high eIF4E levels were associated with progression-free and overall survival reductions [38, 39].

We also found that in U251 cells, H₂O₂-induced OS injury stimulated eIF4E expression. eIF4E has been shown to regulate gene subsets related to key stress reactions, a function that is critical to cancer induction and progression and is usually linked to a substantial increase in eIF4E level to protect cells against ROS accumulation [40]. It has been reported that OS can activate eIF4E, and prolonging eIF4E activation contributes to proliferative responses [41, 42]. Previous reports have linked eIF4E to proliferation- and survival-related protein translation [43, 44]. Furthermore, this study revealed that SOD and GSH-Px in U251 cells were significantly decreased, while MDA and ROS were increased after H₂O₂ stimulation. In addition, with the downregulation of eIF4E, the OS damage caused by H₂O₂ was rescued. SOD, a class of metalloproteins, is one of the most potent antioxidant enzymes [45]. The reduction in SOD activity is related to the destructive effect of O2-superoxide, a compound that accelerates the phosphorylation rate in many carcinogenic signaling processes through the deprotonation of serine or threonine residues, resulting in antiapoptosis effects and tumor progression [46]. GSH-Px is a selenium-dependent enzyme, presenting elevated levels in many cancers, including squamous cell carcinoma [47], colorectal cancer [48], and brain tumors [49]. This can be interpreted as a tumor having high levels of OS, and then, the levels of the body’s antioxidant system increase correspondingly to compensate for the increased ROS levels as a natural defense against cancer [50]. When homeostasis is disturbed, lipid peroxides escape detoxification and produce toxic aldehydes, the most famous of which is malondialdehyde [51]. Moreover, high levels of ROS accumulation are shown to be closely related to programmed cell death. ROS can induce mitochondrial damage and initiate apoptosis. OS-induced cell death is an important factor in many diseases and cell death including cancer. While downregulating eIF4E decreased the ROS level, it promoted H₂O₂-induced apoptosis of glioma U251 cells. We believe that this may be an early self-protection effect in the process of H₂O₂-induced cell damage, which can reduce the ROS accumulation level through the degradation pathway.

However, there is still room for improvement in this study. The role of eIF4E in glioma is only simply revealed, and the underlying pathways and mechanisms are worthy of exploration. Besides, whether eIF4E can regulate the OS sensitivity of glioma in combination with autophagy and other pathways to regulate the apoptosis of glioma cells needs further research.

5. Conclusion

To sum up, this research is the first to demonstrate high eIF4E expression in cancer tissues of LGG and GBM patients and the close connection between high eIF4E levels with adverse prognosis of glioma patients. H₂O₂-induced OS can stimulate eIF4E expression in U251 cells, and downregulating eIF4E can prevent H₂O₂-induced glioma cells from proliferating, invading, and migrating and promote apoptosis.

Conflicts of Interest

The authors declare no competing interests.

Acknowledgments

This study received financial support from the Science and Technology Program of Shenzhen (GJHZ20190821161601670).

Open Research

Data Availability

The labeled dataset used to support the findings of this study are available from the corresponding author upon request.

References

1 Lapointe S., Perry A., and Butowski N. A., Primary brain tumours in adults, The Lancet. (2018) 392, no. 10145, 432–446, https://doi.org/10.1016/S0140-6736(18)30990-5, 2-s2.0-85053731806.
10.1016/S0140-6736(18)30990-5
PubMed Web of Science® Google Scholar
2 Cuddapah V. A., Robel S., Watkins S., and Sontheimer H., A neurocentric perspective on glioma invasion, Nature Reviews Neuroscience. (2014) 15, no. 7, 455–465, https://doi.org/10.1038/nrn3765, 2-s2.0-84903198110, 24946761.
10.1038/nrn3765
CAS PubMed Web of Science® Google Scholar
3 Lang F., Liu Y., Chou F.-J., and Yang C., Genotoxic therapy and resistance mechanism in gliomas, Pharmacology & Therapeutics. (2021) 228, article 107922, https://doi.org/10.1016/j.pharmthera.2021.107922, 34171339.
10.1016/j.pharmthera.2021.107922
PubMed Web of Science® Google Scholar
4 Bi J., Chowdhry S., Wu S., Zhang W., Masui K., and Mischel P. S., Altered cellular metabolism in gliomas -- an emerging landscape of actionable co-dependency targets, Nature Reviews Cancer. (2020) 20, no. 1, 57–70, https://doi.org/10.1038/s41568-019-0226-5, 31806884.
10.1038/s41568-019-0226-5
CAS PubMed Web of Science® Google Scholar
5 Hacioglu C., Kar F., Kacar S., Sahinturk V., and Kanbak G., Bexarotene inhibits cell proliferation by inducing oxidative stress, DNA damage and apoptosis via pparγ/nf-κb signaling pathway in c6 glioma cells, Medical Oncology. (2021) 38, no. 3, 1–11, https://doi.org/10.1007/s12032-021-01476-z.
10.1007/s12032-021-01476-z
Web of Science® Google Scholar
6 Germano I. M. and Binello E., Gene therapy as an adjuvant treatment for malignant gliomas: from bench to bedside, Journal of Neuro-Oncology. (2009) 93, no. 1, 79–87, https://doi.org/10.1007/s11060-009-9869-5, 2-s2.0-65649101289, 19430884.
10.1007/s11060-009-9869-5
CAS PubMed Web of Science® Google Scholar
7 Lara-Velazquez M., Al-Kharboosh R., Jeanneret S., Vazquez-Ramos C., Mahato D., Tavanaiepour D., Rahmathulla G., and Quinones-Hinojosa A., Advances in brain tumor surgery for glioblastoma in adults, Brain Sciences. (2017) 7, no. 12, https://doi.org/10.3390/brainsci7120166, 2-s2.0-85039721377, 29261148.
10.3390/brainsci7120166
PubMed Web of Science® Google Scholar
8 Diamandis P. and Aldape K. D., Insights from molecular profiling of adult glioma, Journal of Clinical Oncology. (2017) 35, no. 21, 2386–2393, https://doi.org/10.1200/JCO.2017.73.9516, 2-s2.0-85024496383, 28640696.
10.1200/JCO.2017.73.9516
CAS PubMed Web of Science® Google Scholar
9 Jia P., Dai C., Cao P., Sun D., Ouyang R., and Miao Y., The role of reactive oxygen species in tumor treatment, RSC Advances. (2020) 10, no. 13, 7740–7750, https://doi.org/10.1039/C9RA10539E, 35492191.
10.1039/C9RA10539E
CAS PubMed Web of Science® Google Scholar
10 Görlach A., Dimova E. Y., Petry A., Martínez-Ruiz A., Hernansanz-Agustín P., Rolo A. P., Palmeira C. M., and Kietzmann T., Reactive oxygen species, nutrition, hypoxia and diseases: problems solved?, Redox Biology. (2015) 6, 372–385, https://doi.org/10.1016/j.redox.2015.08.016, 2-s2.0-84940472278, 26339717.
10.1016/j.redox.2015.08.016
CAS PubMed Web of Science® Google Scholar
11 Reuter S., Gupta S. C., Chaturvedi M. M., and Aggarwal B. B., Oxidative stress, inflammation, and cancer: how are they linked?, Free Radical Biology and Medicine. (2010) 49, no. 11, 1603–1616, https://doi.org/10.1016/j.freeradbiomed.2010.09.006, 2-s2.0-78049370987, 20840865.
10.1016/j.freeradbiomed.2010.09.006
CAS PubMed Web of Science® Google Scholar
12 Sies H., Oxidative stress: a concept in redox biology and medicine, Redox Biology. (2015) 4, 180–183, https://doi.org/10.1016/j.redox.2015.01.002, 2-s2.0-84920903716, 25588755.
10.1016/j.redox.2015.01.002
CAS PubMed Web of Science® Google Scholar
13 Reczek C. R., Birsoy K., Kong H., Martínez-Reyes I., Wang T., Gao P., Sabatini D. M., and Chandel N. S., A crispr screen identifies a pathway required for paraquat-induced cell death, Nature Chemical Biology. (2017) 13, no. 12, 1274–1279, https://doi.org/10.1038/nchembio.2499, 2-s2.0-85034812710, 29058724.
10.1038/nchembio.2499
CAS PubMed Web of Science® Google Scholar
14 Dodson M., Castro-Portuguez R., and Zhang D. D., Nrf2 plays a critical role in mitigating lipid peroxidation and ferroptosis, Redox Biology. (2019) 23, article 101107, https://doi.org/10.1016/j.redox.2019.101107, 2-s2.0-85060432887, 30692038.
10.1016/j.redox.2019.101107
PubMed Web of Science® Google Scholar
15 Redza-Dutordoir M. and Averill-Bates D. A., Activation of apoptosis signalling pathways by reactive oxygen species, Cell Research. (2016) 1863, no. 12, 2977–2992, https://doi.org/10.1016/j.bbamcr.2016.09.012, 2-s2.0-84989154366.
10.1016/j.bbamcr.2016.09.012
CAS Web of Science® Google Scholar
16 Kong Q., Beel J., and Lillehei K., A threshold concept for cancer therapy, Medical Hypotheses. (2000) 55, no. 1, 29–35, https://doi.org/10.1054/mehy.1999.0982, 2-s2.0-0033862305.
10.1054/mehy.1999.0982
CAS PubMed Web of Science® Google Scholar
17 Sonenberg N. and Hinnebusch A. G., Regulation of translation initiation in eukaryotes: mechanisms and biological targets, Cell. (2009) 136, no. 4, 731–745, https://doi.org/10.1016/j.cell.2009.01.042, 2-s2.0-60149091189, 19239892.
10.1016/j.cell.2009.01.042
CAS PubMed Web of Science® Google Scholar
18 Siddiqui N. and Sonenberg N., Signalling to eif4e in cancer, Biochemical Society Transactions. (2015) 43, no. 5, 763–772, https://doi.org/10.1042/BST20150126, 2-s2.0-84947292931, 26517881.
10.1042/BST20150126
CAS PubMed Web of Science® Google Scholar
19 Pettersson F., Del Rincon S. V., Emond A., Huor B., Ngan E., Ng J., Dobocan M. C., Siegel P. M., and Miller W. H., Genetic and pharmacologic inhibition of eif4e reduces breast cancer cell migration, invasion, and metastasis, Cancer Research. (2015) 75, no. 6, 1102–1112, https://doi.org/10.1158/0008-5472.CAN-14-1996, 2-s2.0-84937511731, 25608710.
10.1158/0008-5472.CAN-14-1996
CAS PubMed Web of Science® Google Scholar
20 Culjkovic B. and Borden K. L., Understanding and targeting the eukaryotic translation initiation factor eif4e in head and neck cancer, Journal of Oncology. (2009) 2009, 12, https://doi.org/10.1155/2009/981679, 2-s2.0-73449136900, 981679, 20049173.
10.1155/2009/981679
CAS PubMed Google Scholar
21 Jana S., Deo R., Hough R. P., Liu Y., Horn J. L., Wright J. L., Lam H.-M., Webster K. R., Chiang G. G., Sonenberg N., and Hsieh A. C., Mrna translation is a therapeutic vulnerability necessary for bladder epithelial transformation, JCI Insight. (2021) 6, no. 11, https://doi.org/10.1172/jci.insight.144920, 34032633.
10.1172/jci.insight.144920
PubMed Web of Science® Google Scholar
22 Wang S., Pang T., Gao M., Kang H., Ding W., Sun X., Zhao Y., Zhu W., Tang X., Yao Y., and Hu X., Hpv e6 induces eif4e transcription to promote the proliferation and migration of cervical cancer, FEBS Letters. (2013) 587, no. 6, 690–697, https://doi.org/10.1016/j.febslet.2013.01.042, 2-s2.0-84875218045, 23410891.
10.1016/j.febslet.2013.01.042
CAS PubMed Web of Science® Google Scholar
23 Avdulov S., Li S., Michalek V., Burrichter D., Peterson M., Perlman D. M., Manivel J. C., Sonenberg N., Yee D., and Bitterman P. B., Activation of translation complex eif4f is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells, Cancer Cell. (2004) 5, no. 6, 553–563, https://doi.org/10.1016/j.ccr.2004.05.024, 2-s2.0-2942544833, 15193258.
10.1016/j.ccr.2004.05.024
CAS PubMed Web of Science® Google Scholar
24 Herbert T. P., Fåhraeus R., Prescott A., Lane D. P., and Proud C. G., Rapid induction of apoptosis mediated by peptides that bind initiation factor eif4e, Current Biology. (2000) 10, no. 13, 793–796, https://doi.org/10.1016/S0960-9822(00)00567-4, 2-s2.0-0343167422, 10898981.
10.1016/S0960-9822(00)00567-4
CAS PubMed Web of Science® Google Scholar
25 Dong K., Wang R., Wang X., Lin F., Shen J.-J., Gao P., and Zhang H.-Z., Tumor-specific rnai targeting eif4e suppresses tumor growth, induces apoptosis and enhances cisplatin cytotoxicity in human breast carcinoma cells, Breast Cancer Research and Treatment. (2009) 113, no. 3, 443–456, https://doi.org/10.1007/s10549-008-9956-x, 2-s2.0-58549093201, 18327707.
10.1007/s10549-008-9956-x
CAS PubMed Web of Science® Google Scholar
26 Ge Y., Cheng R., Zhou Y., Shen J., Peng L., Xu X., Dai Q., Liu P., Wang H., Ma X., Jia J., and Chen Z., Cryptotanshinone induces cell cycle arrest and apoptosis of multidrug resistant human chronic myeloid leukemia cells by inhibiting the activity of eukaryotic initiation factor 4e, Molecular and Cellular Biochemistry. (2012) 368, no. 1-2, 17–25, https://doi.org/10.1007/s11010-012-1338-3, 2-s2.0-84864351010, 22614784.
10.1007/s11010-012-1338-3
CAS PubMed Web of Science® Google Scholar
27 Yao Y.-S., Qiu W.-S., Yao R.-Y., Zhang Q., Zhuang L. K., Zhou F., Sun L.-B., and Yue L., Mir-141 confers docetaxel chemoresistance of breast cancer cells via regulation of eif4e expression, Oncology Reports. (2015) 33, no. 5, 2504–2512, https://doi.org/10.3892/or.2015.3866, 2-s2.0-84927153473, 25813250.
10.3892/or.2015.3866
CAS PubMed Web of Science® Google Scholar
28 Truitt M. L., Conn C. S., Shi Z., Pang X., Tokuyasu T., Coady A. M., Seo Y., Barna M., and Ruggero D., Differential requirements for eif4e dose in normal development and cancer, Cell. (2015) 162, no. 1, 59–71, https://doi.org/10.1016/j.cell.2015.05.049, 2-s2.0-84934438925, 26095252.
10.1016/j.cell.2015.05.049
CAS PubMed Web of Science® Google Scholar
29 Gutierrez Sanchez P. A., Babujee L., Jaramillo Mesa H., Arcibal E., Gannon M., Halterman D., Jahn M., Jiang J., and Rakotondrafara A. M., Overexpression of a modified eif4e regulates potato virus y resistance at the transcriptional level in potato, BMC Genomics. (2020) 21, no. 1, 1–16, https://doi.org/10.1186/s12864-019-6423-5.
10.1186/s12864-019-6423-5
Web of Science® Google Scholar
30 McClusky D. R., Chu Q., Yu H., DeBenedetti A., Johnson L. W., Meschonat C., Turnage R., McDonald J. C., Abreo F., and Li B. D., A prospective trial on initiation factor 4e (eif4e) overexpression and cancer recurrence in node-positive breast cancer, Annals of Surgery. (2005) 242, no. 4, 584–592, https://doi.org/10.1097/01.sla.0000184224.55949.90, 2-s2.0-26444587193, 16192819.
10.1097/01.sla.0000184224.55949.90
PubMed Web of Science® Google Scholar
31 Chen C. N., Hsieh F. J., Cheng Y. M., Lee P. H., and Chang K. J., Expression of eukaryotic initiation factor 4e in gastric adenocarcinoma and its association with clinical outcome, Journal of Surgical Oncology. (2004) 86, 22–27, https://doi.org/10.1002/jso.20037, 2-s2.0-1842863109.
10.1002/jso.20037
CAS PubMed Web of Science® Google Scholar
32 Rosenwald I. B., Chen J.-J., Wang S., Savas L., London I. M., and Pullman J., Upregulation of protein synthesis initiation factor eif-4e is an early event during colon carcinogenesis, Oncogene. (1999) 18, no. 15, 2507–2517, https://doi.org/10.1038/sj.onc.1202563, 2-s2.0-0039656540, 10229202.
10.1038/sj.onc.1202563
CAS PubMed Web of Science® Google Scholar
33 Wang R., Geng J., Wang J. H., Chu X. Y., Geng H. C., and Chen L. B., Overexpression of eukaryotic initiation factor 4E (eIF4E) and its clinical significance in lung adenocarcinoma, Lung Cancer. (2009) 66, no. 2, 237–244, https://doi.org/10.1016/j.lungcan.2009.02.001, 2-s2.0-69949189840.
10.1016/j.lungcan.2009.02.001
PubMed Web of Science® Google Scholar
34 Salehi Z., Mashayekhi F., and Shahosseini F., Significance of eif4e expression in skin squamous cell carcinoma, Cell Biology International. (2007) 31, no. 11, 1400–1404, https://doi.org/10.1016/j.cellbi.2007.06.006, 2-s2.0-34548483480, 17689990.
10.1016/j.cellbi.2007.06.006
CAS PubMed Web of Science® Google Scholar
35 Wang S., Rosenwald I. B., Hutzler M. J., Pihan G. A., Savas L., Chen J.-J., and Woda B. A., Expression of the eukaryotic translation initiation factors 4E and 2α in non-Hodgkin’s lymphomas, The American Journal of Pathology. (1999) 155, no. 1, 247–255, https://doi.org/10.1016/S0002-9440(10)65118-8, 2-s2.0-0033031044, 10393856.
10.1016/S0002-9440(10)65118-8
CAS PubMed Web of Science® Google Scholar
36 Fischer P. M., Cap in hand: targeting eif4e, Cell Cycle. (2009) 8, no. 16, 2535–2541, https://doi.org/10.4161/cc.8.16.9301, 2-s2.0-69249222799, 19597330.
10.4161/cc.8.16.9301
CAS PubMed Web of Science® Google Scholar
37 Jia Y., Polunovsky V., Bitterman P. B., and Wagner C. R., Cap-dependent translation initiation factor eIF4E: an emerging anticancer drug target, Medicinal Research Reviews. (2012) 32, no. 4, 786–814, https://doi.org/10.1002/med.21260, 2-s2.0-84863838830, 22495651.
10.1002/med.21260
CAS PubMed Web of Science® Google Scholar
38 Graff J. R., Konicek B. W., Lynch R. L., Dumstorf C. A., Dowless M. S., McNulty A. M., Parsons S. H., Brail L. H., Colligan B. M., Koop J. W., Hurst B. M., Deddens J. A., Neubauer B. L., Stancato L. F., Carter H. W., Douglass L. E., and Carter J. H., Eif4e activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival, Cancer Research. (2009) 69, no. 9, 3866–3873, https://doi.org/10.1158/0008-5472.CAN-08-3472, 2-s2.0-65949111747.
10.1158/0008-5472.CAN-08-3472
CAS PubMed Web of Science® Google Scholar
39 Coleman L., Peter M., Teall T., Brannan R., Hanby A., Honarpisheh H., Shaaban A., Smith L., Speirs V., Verghese E., McElwaine J. N., and Hughes T. A., Combined analysis of eif4e and 4e-binding protein expression predicts breast cancer survival and estimates eif4e activity, British Journal of Cancer. (2009) 100, no. 9, 1393–1399, https://doi.org/10.1038/sj.bjc.6605044, 2-s2.0-65549108194, 19367274.
10.1038/sj.bjc.6605044
CAS PubMed Web of Science® Google Scholar
40 Mittler R., Ros are good, Trends in Plant Science. (2017) 22, no. 1, 11–19, https://doi.org/10.1016/j.tplants.2016.08.002, 2-s2.0-84994402047.
10.1016/j.tplants.2016.08.002
CAS PubMed Web of Science® Google Scholar
41 Duncan R. F., Peterson H., and Sevanian A., Signal transduction pathways leading to increased eif4e phosphorylation caused by oxidative stress, Free Radical Biology and Medicine. (2005) 38, no. 5, 631–643, https://doi.org/10.1016/j.freeradbiomed.2004.09.034, 2-s2.0-15744405797, 15683719.
10.1016/j.freeradbiomed.2004.09.034
CAS PubMed Web of Science® Google Scholar
42 Furic L., Rong L., Larsson O., Koumakpayi I. H., Yoshida K., Brueschke A., Petroulakis E., Robichaud N., Pollak M., Gaboury L. A., Pandolfi P. P., Saad F., and Sonenberg N., Eif4e phosphorylation promotes tumorigenesis and is associated with prostate cancer progression, Proceedings of the National Academy of Sciences. (2010) 107, no. 32, 14134–14139, https://doi.org/10.1073/pnas.1005320107, 2-s2.0-77956275419, 20679199.
10.1073/pnas.1005320107
CAS PubMed Web of Science® Google Scholar
43 Culjkovic B., Topisirovic I., Skrabanek L., Ruiz-Gutierrez M., and Borden K. L., Eif4e promotes nuclear export of cyclin d1 mrnas via an element in the 3′ utr, The Journal of Cell Biology. (2005) 169, no. 2, 245–256, https://doi.org/10.1083/jcb.200501019, 2-s2.0-18544363908.
10.1083/jcb.200501019
CAS PubMed Web of Science® Google Scholar
44 Li S., Takasu T., Perlman D. M., Peterson M. S., Burrichter D., Avdulov S., Bitterman P. B., and Polunovsky V. A., Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release∗, Journal of Biological Chemistry. (2003) 278, no. 5, 3015–3022, https://doi.org/10.1074/jbc.M208821200, 2-s2.0-0037474323, 12441348.
10.1074/jbc.M208821200
CAS PubMed Web of Science® Google Scholar
45 Yi J.-F., Li Y.-M., Liu T., He W.-T., Li X., Zhou W.-C., Kang S.-L., Zeng X.-T., and Zhang J.-Q., Mn-sod and cuzn-sod polymorphisms and interactions with risk factors in gastric cancer, World Journal of Gastroenterology: WJG. (2010) 16, no. 37, 4738–4746, https://doi.org/10.3748/wjg.v16.i37.4738, 2-s2.0-77957723632, 20872977.
10.3748/wjg.v16.i37.4738
CAS PubMed Web of Science® Google Scholar
46 Bize I. B., Oberley L. W., and Morris H. P., Superoxide dismutase and superoxide radical in morris hepatomas, Cancer Research. (1980) 40, no. 10, 3686–3693, 6254638.
CAS PubMed Web of Science® Google Scholar
47 Deshpande K. C., Kulkarni M. M., and Rajput D. V., Evaluation of glutathione peroxidase in the blood and tumor tissue of oral squamous cell carcinoma patients, Journal of Oral and Maxillofacial Pathology: JOMFP. (2018) 22, no. 3, https://doi.org/10.4103/jomfp.JOMFP_140_17, 30651704.
10.4103/jomfp.JOMFP_140_17
PubMed Google Scholar
48 Lee F., Vessey A., Rofstad E., Siemann D., and Sutherland R., Heterogeneity of glutathione content in human ovarian cancer, Cancer Research. (1989) 49, no. 19, 5244–5248, 2766292.
CAS PubMed Web of Science® Google Scholar
49 Kudo H., Mio T., Kokunai T., Tamaki N., Sumino K., and Matsumoto S., Quantitative analysis of glutathione in human brain tumors, Journal of Neurosurgery. (1990) 72, no. 4, 610–615, https://doi.org/10.3171/jns.1990.72.4.0610, 2-s2.0-0025374085.
10.3171/jns.1990.72.4.0610
CAS PubMed Web of Science® Google Scholar
50 Strycharz-Dudziak M., Kiełczykowska M., Drop B., Świątek Ł., Kliszczewska E., Musik I., and Polz-Dacewicz M., Total antioxidant status (tas), superoxide dismutase (sod), and glutathione peroxidase (gpx) in oropharyngeal cancer associated with ebv infection, Oxidative Medicine and Cellular Longevity. (2019) 2019, 15, https://doi.org/10.1155/2019/5832410, 2-s2.0-85070800460, 5832410.
10.1155/2019/5832410
PubMed Web of Science® Google Scholar
51 Singh M., Shrivastava D., and Kale R., Antioxidant potential of asparagus adscendens, Antioxidant Enzyme. (2012) 323, https://doi.org/10.5772/52983.
10.5772/52983
Google Scholar

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Expression of eIF4E Gene in Glioma and Its Sensitivity to Oxidative Stress

Abstract

1. Introduction

2. Data and Methods