Tissue and Serum Thioredoxin System and miR-21, miR-23a/b and let-7a as Potential Biomarkers for Brain Tumor Progression

doi:10.21203/rs.3.rs-967661/v1

Download PDF

Research Article

Tissue and Serum Thioredoxin System and miR-21, miR-23a/b and let-7a as Potential Biomarkers for Brain Tumor Progression

https://doi.org/10.21203/rs.3.rs-967661/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted 15 Oct, 2021

You are reading this latest preprint version

Thioredoxin system and miRNAs are potential targets for both cancer progression and treatment. However, role of miRNAs and their relation between the expression profile of thioredoxin system in brain tumor progression remains unclear. Thus, in this study we aimed to determine the expression profiles of redox components Trx-1, TrxR-1 and PRDX-1, and oncogenic miR-21, miR-23a/b and let-7a and oncosuppressor miR-125 in different brain tumor tissues and their association with increasing tumor grade. We studied Trx-1, TrxR-1 and PRDX-1 mRNA expression levels by quantitative real-time polymerase chain reaction (qRT-PCR) and protein levels by Western blot and miR-23a, miR-23b, miR-125a, miR-21 and let-7a miRNA expression levels by qRT-PCR in 16 glioma, 15 meningioma, 5 metastatic and 2 benign tumor samples. We also examined Trx-1, TrxR-1 and PRDX-1 protein levels in serum samples of 36 brain tumor patients and 37 healthy volunteers by ELISA. We found that Trx-1, TrxR-1 and PRDX-1 presented high mRNA expression but low protein expression in low-grade brain tumor tissues whereas they showed higher protein expression in sera of patients with low-grade brain tumors. miR-23b, miR-21, miR-23a and let-7a were highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity. Our findings showed that Trx-1, TrxR-1 and PRDX-1 and miR-21, miR-23a/b, and let-7a might be used for brain tumor diagnosis in the clinic. Further prospective studies including molecular pathway analyses are required to validate the miRNA/thioredoxin system regulatory axis in brain tumor progression.

Cellular & Molecular Neuroscience

Neurology

Thioredoxin system

MicroRNA (miRNA)

Brain tumor progression

Biomarker

Brain tumors are diagnosed both in adults and children which lead to high mortality and morbidity worldwide [1–3]. 1.6% new cases and 2.5% deaths of brain tumors globally have been reported in 2020 [4]. Malignant glioma and meningiomas are the most common types among all brain tumors [2]. Magnetic resonance imaging and various molecular diagnostic markers are in use for patients with brain tumor in the clinic [5]. However, distinguishing primary and metastatic tumors is challenging with these methods [6]. Therefore, novel diagnostic biomarkers remain under investigation.

Oxidative stress is a key feature of cancer progression which involves the increased reactive oxygen species (ROS) and antioxidant response [7–9]. Thioredoxin (Trx) system is a crucial cytoplasmic antioxidant system which comprises Trx-1, thioredoxin reductase-1 (TrxR-1) and NADPH [9]. Trx-1 and/or TrxR-1 levels are highly expressed in various human cancers[9–13] including brain tumors [14–18] when compared to healthy ones which are also associated with cancer cell growth, proliferation, invasion, metastasis and prognosis [19, 20]. Peroxiredoxin (PRDX) family is involved in cellular homeostasis and redox system which is responsible for antioxidant and cell death mechanism activation by interacting with Trx system [21–23]. High PRDX-1 expression has been shown in human glioma cells by inhibiting apoptosis of U87MG cells [24] and 293T cells by preventing PTEN oxidation and Akt activation [25] in vitro. PRDX-1 knockdown induces apoptosis and reduces glioma cell proliferation in vitro [26].

MicroRNAs (miRNAs) are small noncoding RNAs regulating mRNA expression levels and functions of target genes as protooncogenes or oncosuppressor genes [27–29]. MiRNAs are linked with cell metabolism, proliferation, apoptosis and survival [27, 28]. In brain tumors, expression of protooncogenes are elevated whereas expression of oncosuppressor miRNAs are reduced [30]. Recent studies showed that expression of several miRNAs including miR-21 [31, 27], miR-23a [31–33, 22], miR-23b [33] increased whereas miR-101 [34], miR-204 [35], miR-128 [36] and miR-135a [37] expressions decreased in brain tumor tissues mostly constituting glioma or meningioma cases. Relation between miRNAs and brain tumors have been implicated in numerous studies [38–43, 31, 44, 32, 35, 34]. Moreover, a large number of studies shows that several miRNAs regulate proliferation, migration and invasion of different types of tumor cells through thioredoxin and/or peroxiredoxin families[45–54]. However, limited number of studies regarding the relation between miRNAs and thioredoxin system components in brain tumors take place in the literature [38, 39]. Tumor suppressor miR-17 levels have been correlated with TrxR-2 downregulation in T98G glioblastoma multiforme cells in vitro [38]. Anti-oncogenic miR-383 was downregulated in medulloblastoma cells by inhibiting PRDX-3 protein expression [39]. In addition, redox status including ROS accumulation regulates production or inhibition of miR-21, miR-23b and miR-125a [53] through Nrf2/ARE [55] and Phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) [56] pathways in various tumor cells. These studies show that thioredoxin system components and miRNAs are potential targets for both cancer progression and treatment. Still, role of miRNAs and their relation between the expression profile of thioredoxin system components in brain tumor progression remains unclear. Thus, in this study we hypothesized that redox components including Trx-1, TrxR-1 and PRDX-1 might have a relation with oncogenic miR-21, miR-23a/b and let-7a and tumor suppressor miR-125a levels which both having a codependent relationship among Nrf2/ARE and PI3K/Akt pathways. As a preliminary study, we aimed to determine the expression profiles of Trx-1, TrxR-1, PRDX-1, oncogenic miR-21, miR-23a/b and let-7a and oncosuppressor miR-125 in different brain tumor tissues and their association with increasing tumor grade.

Herein, we studied Trx-1, TrxR-1 and PRDX-1 mRNA expression levels by quantitative real-time polymerase chain reaction (qRT-PCR) and protein levels by Western blot and miR-23a, miR-23b, miR-125a, miR-21 and let-7a miRNA expression levels by qRT-PCR in 16 glioma, 15 meningioma, 5 metastatic and 2 benign tumor samples. We also examined Trx-1, TrxR-1 and PRDX-1 protein levels in serum samples of 36 brain tumor patients and 37 healthy volunteers by ELISA. We found that Trx-1, TrxR-1 and PRDX-1 presented high mRNA expression but low protein expression in low-grade brain tumor tissues whereas they showed higher protein expression in sera of patients with low-grade brain tumors. miR-23b, miR-21, miR-23a and let-7a were highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity. Our findings enhanced the understanding of the relation between miRNAs and thioredoxin system activity. Moreover, miR-23a/b, miR-21 and let-7a might be utilized as diagnostic and prognostic markers for brain tumor patients and potential therapeutic targets for its treatment in the clinic.

Ethics Statement and Sample Collection

This research was carried out with Medicana International Ankara Hospital Research Ethics Committee approval (#21102019/04). Brain tumor samples were surgically resected from 38 patients who underwent surgery at Medicana International Ankara Hospital from January 2020 to October 2020. All patients obtained written informed consents. The brain tumors were classified according to World Health Organization (WHO) criteria [57]. 16 of these tumors were low- and high-grade glioma (WHO grade I and II; grade III and IV, respectively), 15 were low- and high-grade meningioma (WHO grade I and II; grade III and IV, respectively), 5 were metastatic tumors and 2 were other benign tumors. Clinicopathological features of tumor samples are listed in Table 1. Serum samples of 36 brain tumor patients and of 37 healthy volunteers were also obtained. 13 of these volunteers were at the age 35 and below, 20 were ages between 36-56 and 4 were at the age of 57 and over. Minimum required number of samples and replicates were revealed by power analysis using G-Power.

Table 1

Clinicopathological features of brain tumors of patients.
Patient Characteristic	Patients (n=38) (%)
Age (Years)	53.78 ± 14.99
≤35	4 (10.53%)
36-56	15 (39.47%)
≥57	19 (50.00%)
Gender
Male	21 (55.26%)
Female	17 (44.74%)
Type of Brain Tumor with Clinical Stage
Glioma (Stage I-IV)	16 (42.11%)
Meningioma (Stage I-IV)	15 (39.47%)
Metastasis	5 (13.16%)
Other benign primary tumors	2 (5.26%)

A randomized observative study including control and experimental groups was carried out. All control and experimental groups were independent variables whereas mRNA, miRNA and protein expression results, were defined as dependent variables.

Quantitative Real-time Polymerase Chain Reaction (qRT-PCR)

Trx-1, TrxR-1 and PRDX-1 mRNA expression levels were determined in human brain tumor samples by qRT-PCR [15, 24, 9]. 100 mg of brain tissues were homogenized with 1 ml TRIzol (RiboEx, #301-001, GeneAll, South Korea) by hand-held homogenizer (#MT-30K, Miulab, China). Total RNA was isolated by mRNA isolation kit (#305-101, GeneAll, South Korea) and concentrations and purities of RNA samples were measured via NanoDrop spectrophotometer (NanoDrop 1000, ThermoScientific, USA) at 260-280 nm wavelength. cDNA was synthesized (#W2211, Wizbio Solutions, South Korea) and qRT-PCR was done on Biorad instrument (CFX Connect, Biorad, USA). Relative mRNA expression was determined by WizPure qPCR SYBR Green Master Mix (#W1711, Wizbio Solutions, South Korea) fluorescent dye.

miR-23a/b, miR-125a, miR-21 and let-7a miRNA expression levels were determined by homogenizing 50 mg of brain tissues with 500 µl TRIzol via hand-held homogenizer. Total miRNA was isolated by miRNA isolation kit (#325-150, GeneAll, South Korea) and concentration and purity of miRNA were measured. cDNA synthesis was accomplished using stem-loop transcriptase primers and relative miRNA expression was assessed as performed for relative mRNA expression. All mRNA and miRNA levels were normalized to house-keeping gene GAPDH[58] (n=30 in total) and relative fold change was analyzed according to 2^−ΔΔCt. Primer sequences were summed-up in Table 2.

Table 2

Primer sequences designed for qRT-PCR.
Gene		Oligonucleotide Sequence
GAPDH	Forward	5’-GGTGTGAACCATGAGAAGTATGA-3’
GAPDH	Reverse	5’-GAGTCCTTCCACGATACCAAG-3’
Trx-1 (TXN)	Forward	5′-CAACCCTTTCTTTCATTCCCTCT-3′
Trx-1 (TXN)	Reverse	5′-CACCCACCTTTTGTCCCTTCT-3′
TrxR-1 (TXNRD1)	Forward	5’-GTTGCCAAGACTGCAAACCAC-3’
TrxR-1 (TXNRD1)	Reverse	5’-CCCTGCCAAATGTCAGCTTC-3’
PRDX1	Forward	5’-GCACCATTGCTCAGGATTATG-3’
PRDX1	Reverse	5’-GCCAACAGGGAGGTCATTTAC-3’
miR-23a	ST-primer	5’-GAAAGAAGGCGAG…TAGG-3’
miR-23a	Forward	5’-ATCACATTGCCAGGGATTTCC-3’
miR-23b	ST-primer	5’-GAAAGAAGGCGAG…ATTA-3’
miR-23b	Forward	5’-ATCACATTGCCAGGGATTACCAC-3’
miR-125a	ST-primer	5’-GAAAGAAGGCGAG…TCCA-3’
miR-125a	Forward	5’-TCCCTGAGACCCTTTAACCTGTGA-3’
miR-21	ST-primer	5’-GAAAGAAGGCGAG…GTAG-3’
miR-21	Forward	5’-TAGCTTATCAGACTGATGTTGA-3’
let-7a	ST-primer	5’-GAAAGAAGGCGAG…TATG-3’
let-7a	Forward	5’-TCCCTGAGACCCTTTAACCTGTGA-3’
Universal Primer	Reverse	5’-CGAGGAAGAAGACGGAAGAAT-3’

Western blot

30 mg brain tumor tissues (n=31 in total) were lysed with RIPA buffer (#R0278-50ML, Sigma-Aldrich, Germany) containing protease inhibitor (ProBlock™ Gold Mammalian Protease Inhibitor Cocktail [100x], #GB-331-1, Gold Biotechnology, USA) by hand-held homogenizer and total protein content was calculated by BCA test (Pierce™ BCA Protein Assay Kit, #23225, ThermoScientific, USA) at 562 nm wavelength. Extracted proteins were separated by 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE, Mini-PROTEAN® Electrophoresis Cell, #1658004, Biorad, USA), subsequently transferred onto poly(vinylidene fluoride) membrane via transfer blot system (Trans-Blot Turbo Transfer System, #1704150, Biorad, USA). Following 2 hours of pre-blocking step (5% non-fat milk), membranes were kept overnight with rabbit anti-human Trx-1 (1:500, #bs-50523R, Bioss Antibodies, USA), TrxR-1 (1:500, #bs-8299R, Bioss Antibodies, USA), PRDX-1 (1:500, #bs-3875R, Bioss Antibodies, USA) and GAPDH (house-keeping gene, 1:500, #bs-2188R, Bioss Antibodies, USA) primary antibodies, then washed in TBS-t and kept with horseradish peroxidase-conjugated IgG as secondary antibody (#BT-AS00010, Bioassay Technology Laboratory, China) for 1 hour at room temperature. Enhanced chemiluminescent (ECL) was applied for visualization of bands via chemiluminescence imaging system (ChemiDoc Imaging System, #12003153, Biorad, USA). Bands were analyzed by Image Lab Software (v6.0, Biorad).

Enzyme-Linked ImmunoSorbent Assay (ELISA)

Human Trx-1 (#E1452Hu), TrxR-1 (#E3953Hu) and PRDX-1 (#E2924Hu) (all from Bioassay Technology Laboratory, China) protein concentrations in sera of brain tumor patients and healthy volunteers were evaluated by ELISA following manufacturer’s guideline. Briefly, standard solutions and samples were added to 96-well plate and biotinylated primary antibodies and streptavidin-HRP were added to wells respectively. Plates were then incubated 60 minutes at 37 ^oC. Subsequently, plates were washed with wash buffer; incubated with substrate solutions for 10 minutes at 37 ^oC in the dark recommended in guideline. After adding stop solution to wells, color change from blue to yellow was determined and optical density of each well was measured by plate reader (SPECTROstar® Omega, BMG LABTECH, Germany) at 450 nm. Each serum sample was studied triplicate and protein levels in serum samples of brain tumor patients (n=36) were compared with that of healthy volunteers (n=37).

Statistical Analysis

Data used for qRT-PCR and Western blot data exhibited normal distribution whereas ELISA data presented non-normal distribution by Shapiro-Wilk test. Pairwise comparison of qRT-PCR results was subjected to Student’s t-test. Western blot results were analyzed with one-way analysis of variance (ANOVA) and Tukey’s HSD tests. Two-sample Kolmogorov-Smirnov test was used for comparison of nonparametric results in ELISA. Pearson correlation test was conducted for qRT-PCR. Whole data were analyzed within 95% confidence interval.

Thioredoxin system components showed higher mRNA expression but low protein expression in low-grade brain tumor tissues

TrxR-1 mRNA expression was higher in all brain tumor tissues compared to control group (Fig. 1A) by qRT-PCR. Trx-1 and TrxR-1 mRNA expressions were higher in low-grade meningioma tissues than that of high-grade meningioma (Fig. 1B) but vice versa for protein expressions by Western blot (Fig. 1C). Similarly, high-grade glioma tissues had higher Trx-1 and TrxR-1 protein expressions than that in low-grade glioma by Western blot (Fig. 1C). There was no significant difference in Trx-1, TrxR-1 and PRDX-1 mRNA expression levels between high- and low-grade glioma patients (Fig. 1B). Trx-1, TrxR-1 and PRDX-1 mRNA expression levels were lower in other benign primary tumors when compared to metastatic tumors (Fig. 1B). However, metastatic tumors had lower Trx-1 and TrxR-1 protein expression compared with high-grade glioma and high-grade meningioma by Western blot.

Thioredoxin system components showed higher protein expression in serum samples of patients with low-grade brain tumors

Sera of brain tumor patients had significantly lower Trx-1 (Fig. 1D) and TrxR-1 (Fig. 1E) protein expressions comparing to serum samples of healthy volunteers by ELISA. No significant difference was observed in PRDX-1 protein expression between the two groups (Fig. 1F). Serum samples of high-grade glioma patients had significantly lower Trx-1 (Fig. 1G), TrxR-1 (Fig. 1H) and PRDX-1 (Fig. 1I) protein expressions than that in low-grade glioma patients. Serum samples of patients with high-grade meningioma and other benign primary tumors had significantly lower Trx-1 (Fig. 1G) and TrxR-1 (Fig. 1H) protein expressions when compared to low-grade meningioma and metastatic tumors, respectively. Sera of healthy volunteers had significantly higher Trx-1 and TrxR-1 protein expressions than all groups by ELISA (Fig. 1G, H). PRDX-1 protein expression level was significantly higher in healthy volunteers when compared to sera of patients with high-grade meningioma, metastatic tumor or other benign primary tumors (Fig. 1I).

miR-23a/b, miR-21 and let-7a are highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity

miR-23a/b, miR-21 and let-7a expression levels were greater in all brain tumor tissues when compared to control group (Fig. 2A) by qRT-PCR. No significant difference was noticed between the groups for miR-125a expression by qRT-PCR. Low-grade meningioma tissues had significantly higher miR-23b, miR-21, miR-23a and let-7a miRNA expression levels than that of high-grade meningioma (Fig. 2B). miR-21 and let-7a expressions were lower in other primary benign tumors when compared to metastatic tumors (Fig. 2B). There was no significant alteration in miR-125a miRNA expression levels among all groups by qRT-PCR.

Trx-1, TrxR-1 and PRDX-1 mRNA expression levels are positively correlated with miR-125, miR-23b, miR-21, miR-23a and let-7a miRNA expressions in brain tumor tissues (Fig. 1C) by Pearson correlation analysis.

In this study, we showed that thioredoxin system components had higher expression in low-grade brain tumor samples also having a strong positive correlation with oncogenic miR-21, miR-23a/b and let-7a and tumor suppressor miR-125a levels for the first time. We examined high mRNA and low protein expressions of Trx-1 and TrxR-1 in low-grade meningioma and benign primary tumor tissues when compared to high-grade meningioma and metastatic tumor tissues, respectively by qRT-PCR and high Trx-1 and TrxR-1 protein expressions in high-grade glioma comparing to low-grade glioma by Western blot. Our findings regarding the increase in Trx-1[9, 16, 18, 59] and TrxR-1 [14, 16, 18] protein expression with the increasing tumor grade are consistent with the other findings of prior studies showing poor clinical outcome for patients with brain tumor. Metastatic tumor samples had significantly higher PRDX-1 mRNA expression compared to benign primary tumors, however, serum samples of all brain tumor patients had lower PRDX-1 expression than that of healthy volunteers. PRDX-1 was up-regulated in various cancer cells [60–62] to regulate cell growth and apoptosis through ROS-dependent pathway [63]. Thus, our results regarding qRT-PCR were coherent with the literature [24, 63]. However, various studies revealed that PRDX-1 may induce apoptosis of tumor cells [63–65]. Herein, lower level of PRDX-1 protein in sera of brain tumor patients might show that decrease in PRDX-1 promotes the proliferation and invasion of tumor cells [64, 65]. Our finding on PRDX-1 revealed that it may act as either oncogenic or tumor suppressor protein.

Here we report that miR-23a/b, miR-21 and let-7a expression levels were greater in low-grade meningioma comparing to high-grade meningioma. miR-21 [66, 28, 67, 27, 42, 41, 43], miR-23a [68, 69, 27, 70, 32], miR-23b [68, 69] and let-7a [67, 71, 72] is have oncogenic capability in various tumor cells including brain tumors [73, 74, 44]. Thus, our findings imply that those miRNAs might be potential biomarkers for diagnosis of meningioma. Herein, we also found that miR-21 and let-7a expressions were greater in metastatic tumors when compared to other primary benign tumor tissues showing a positive correlation between miRNA expressions and tumor grade. Trx-1, TrxR-1 and PRDX-1 mRNA expression levels were positively correlated with miR-21, miR-23a/b, miR-125, and let-7a expressions in brain tumor tissues by Pearson correlation analysis. Kalinina et al demonstrated high correlation between the antioxidant protection including thioredoxins and peroxiredoxins and miRNAs [75] which also support our results. PRDX-3 was linked with miR-23b for human prostate cancer progression [49]. Similarly, miR-23a and miR-23b regulate TrxR-1 expression during skeletal muscle differentiation [76]. Our key findings may implicate the diagnostic value of miR-21, miR-23a/b, let-7a and thioredoxin system components for brain tumors which also improve the understanding in determining the levels of biomarkers in different brain tumor grades.

In the current study, a correlation analysis has been done for the relation between thioredoxin system components and various miRNAs as oncogenes in brain tumor tissues and serum samples of patients, however, in vitro and in vivo functional studies including the association between miRNAs and redox system through Nrf2/ARE [55] and PI3K/Akt [56] pathways must be performed for the miRNA/thioredoxin system regulatory axis in brain tumor progression which generates a crucial limitation for this study. This limitation, still, does not hinder our further studies since the expression and correlation profiles in thioredoxin system and miRNAs would facilitate in-depth studies for better understanding of miRNA and redox system component functions as novel biomarkers. Since this research has been conducted with human subjects, brain tissue samples could not be obtained from healthy volunteers. To cope with this limitation, we compared levels of thioredoxin system components with metastatic and/or other benign tumors for qRT-PCR and Western blot and serum samples of healthy volunteers for ELISA.

Taken together, our findings show that thioredoxin system components including Trx-1, TrxR-1 and PRDX-1 and miR-21, miR-23a/b, and let-7a could be potential biomarkers together for brain tumor diagnosis especially for meningioma cases. Further prospective studies are needed to validate their relation and its projection to brain tumor treatment in the clinic.

Acknowledgements

Authors would like to thank Dr. Esra Elmalı for her help of obtaining the human subjects in Medicana International Ankara Hospital.

Author Contributions

Kilic N., Boyacioglu O. and Turna Saltoglu G. contributed to the design of the work and conducted the experiments. Kurt G. and Bulduk E.B. obtained the human subjects. Kilic N., Boyacioglu O. and Korkusuz P. analyzed and interpreted of whole data and completed drafting and revising the manuscript. All authors agreed on the accuracy of any part of the work which have been appropriately investigated and finally approved the manuscript to be published.

Funding

This study was granted by Atılım University Scientific Research Projects Coordination Unit (ARGEDA Technology Transfer Office, #ADP1920-06).

Conflict of Interest

Authors declare that they have no relevant or material financial interests relating to the research.

Patel AP, Fisher JL, Nichols E, Abd-Allah F, Abdela J, Abdelalim A, Abraha HN, Agius D, Alahdab F, Alam T, Allen CA, Anber NH, Awasthi A, Badali H, Belachew AB, Bijani A, Bjørge T, Carvalho F, Catalá-López F, Choi J-YJ, Daryani A, Degefa MG, Demoz GT, Do HP, Dubey M, Fernandes E, Filip I, Foreman KJ, Gebre AK, Geramo YCD, Hafezi-Nejad N, Hamidi S, Harvey JD, Hassen HY, Hay SI, Irvani SSN, Jakovljevic M, Jha RP, Kasaeian A, Khalil IA, Khan EA, Khang Y-H, Kim YJ, Mengistu G, Mohammad KA, Mokdad AH, Nagel G, Naghavi M, Naik G, Nguyen HLT, Nguyen LH, Nguyen TH, Nixon MR, Olagunju AT, Pereira DM, Pinilla-Monsalve GD, Poustchi H, Qorbani M, Radfar A, Reiner RC, Roshandel G, Safari H, Safiri S, Samy AM, Sarvi S, Shaikh MA, Sharif M, Sharma R, Sheikhbahaei S, Shirkoohi R, Singh JA, Smith M, Tabarés-Seisdedos R, Tran BX, Tran KB, Ullah I, Weiderpass E, Weldegwergs KG, Yimer EM, Zadnik V, Zaidi Z, Ellenbogen RG, Vos T, Feigin VL, Murray CJL, Fitzmaurice C (2019) Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 18 (4):376-393. doi:10.1016/S1474-4422(18)30468-X
McNeill KA (2016) Epidemiology of Brain Tumors. Neurol Clin 34 (4):981-998. doi:https://doi.org/10.1016/j.ncl.2016.06.014
Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Fleming T, Forouzanfar MH, Hancock J, Hay RJ, Hunter-Merrill R, Huynh C, Hosgood HD, Johnson CO, Jonas JB, Khubchandani J, Kumar GA, Kutz M, Lan Q, Larson HJ, Liang X, Lim SS, Lopez AD, MacIntyre MF, Marczak L, Marquez N, Mokdad AH, Pinho C, Pourmalek F, Salomon JA, Sanabria JR, Sandar L, Sartorius B, Schwartz SM, Shackelford KA, Shibuya K, Stanaway J, Steiner C, Sun J, Takahashi K, Vollset SE, Vos T, Wagner JA, Wang H, Westerman R, Zeeb H, Zoeckler L, Abd-Allah F, Ahmed MB, Alabed S, Alam NK, Aldhahri SF, Alem G, Alemayohu MA, Ali R, Al-Raddadi R, Amare A, Amoako Y, Artaman A, Asayesh H, Atnafu N, Awasthi A, Saleem HB, Barac A, Bedi N, Bensenor I, Berhane A, Bernabé E, Betsu B, Binagwaho A, Boneya D, Campos-Nonato I, Castañeda-Orjuela C, Catalá-López F, Chiang P, Chibueze C, Chitheer A, Choi JY, Cowie B, Damtew S, das Neves J, Dey S, Dharmaratne S, Dhillon P, Ding E, Driscoll T, Ekwueme D, Endries AY, Farvid M, Farzadfar F, Fernandes J, Fischer F, TT GH, Gebru A, Gopalani S, Hailu A, Horino M, Horita N, Husseini A, Huybrechts I, Inoue M, Islami F, Jakovljevic M, James S, Javanbakht M, Jee SH, Kasaeian A, Kedir MS, Khader YS, Khang YH, Kim D, Leigh J, Linn S, Lunevicius R, El Razek HMA, Malekzadeh R, Malta DC, Marcenes W, Markos D, Melaku YA, Meles KG, Mendoza W, Mengiste DT, Meretoja TJ, Miller TR, Mohammad KA, Mohammadi A, Mohammed S, Moradi-Lakeh M, Nagel G, Nand D, Le Nguyen Q, Nolte S, Ogbo FA, Oladimeji KE, Oren E, Pa M, Park EK, Pereira DM, Plass D, Qorbani M, Radfar A, Rafay A, Rahman M, Rana SM, Søreide K, Satpathy M, Sawhney M, Sepanlou SG, Shaikh MA, She J, Shiue I, Shore HR, Shrime MG, So S, Soneji S, Stathopoulou V, Stroumpoulis K, Sufiyan MB, Sykes BL, Tabarés-Seisdedos R, Tadese F, Tedla BA, Tessema GA, Thakur JS, Tran BX, Ukwaja KN, Uzochukwu BSC, Vlassov VV, Weiderpass E, Wubshet Terefe M, Yebyo HG, Yimam HH, Yonemoto N, Younis MZ, Yu C, Zaidi Z, Zaki MES, Zenebe ZM, Murray CJL, Naghavi M (2017) Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 3 (4):524-548. doi:10.1001/jamaoncol.2016.5688
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians 71 (3):209-249. doi:https://doi.org/10.3322/caac.21660
Aldape K, Brindle KM, Chesler L, Chopra R, Gajjar A, Gilbert MR, Gottardo N, Gutmann DH, Hargrave D, Holland EC, Jones DTW, Joyce JA, Kearns P, Kieran MW, Mellinghoff IK, Merchant M, Pfister SM, Pollard SM, Ramaswamy V, Rich JN, Robinson GW, Rowitch DH, Sampson JH, Taylor MD, Workman P, Gilbertson RJ (2019) Challenges to curing primary brain tumours. Nat Rev Clin Oncol 16 (8):509-520. doi:10.1038/s41571-019-0177-5
Kan LK, Drummond K, Hunn M, Williams D, O'Brien TJ, Monif M (2020) Potential biomarkers and challenges in glioma diagnosis, therapy and prognosis. BMJ neurol open 2 (2):e000069. doi:10.1136/bmjno-2020-000069
Jelic M, Mandic A, Maricic S, Srdjenovic B (2021) Oxidative stress and its role in cancer. J Cancer Res Ther 17 (1):22-28. doi:10.4103/jcrt.JCRT_862_16
Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97:55-74. doi:10.1016/j.ejmech.2015.04.040
Bhatia M, McGrath KL, Di Trapani G, Charoentong P, Shah F, King MM, Clarke FM, Tonissen KF (2016) The thioredoxin system in breast cancer cell invasion and migration. Redox biology 8:68-78. doi:https://doi.org/10.1016/j.redox.2015.12.004
Kilic N, Yavuz Taslipinar M, Guney Y, Tekin E, Onuk E (2014) An investigation into the serum thioredoxin, superoxide dismutase, malondialdehyde, and advanced oxidation protein products in patients with breast cancer. Ann Surg Oncol 21 (13):4139-4143. doi:10.1245/s10434-014-3859-3
Raninga PV, Trapani GD, Vuckovic S, Bhatia M, Tonissen KF (2015) Inhibition of thioredoxin 1 leads to apoptosis in drug-resistant multiple myeloma. Oncotarget 6 (17)
Grogan TM, Fenoglio-Prieser C, Zeheb R, Bellamy W, Frutiger Y, Vela E, Stemmerman G, Macdonald J, Richter L, Gallegos A, Powis G (2000) Thioredoxin, a putative oncogene product,is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival. Hum Pathol 31 (4):475-481. doi:https://doi.org/10.1053/hp.2000.6546
Ceccarelli J, Delfino L, Zappia E, Castellani P, Borghi M, Ferrini S, Tosetti F, Rubartelli A (2008) The redox state of the lung cancer microenvironment depends on the levels of thioredoxin expressed by tumor cells and affects tumor progression and response to prooxidants. Int J Cancer Res 123 (8):1770-1778. doi:https://doi.org/10.1002/ijc.23709
Esen H, Feyzioglu B, Erdi F, Keskin F, Kaya B, Demir LS (2015) High thioredoxin reductase 1 expression in meningiomas undergoing malignant progression. Brain Tumor Pathol 32 (3):195-201. doi:10.1007/s10014-015-0212-x
Esen H, Erdi F, Kaya B, Feyzioglu B, Keskin F, Demir LS (2015) Tissue thioredoxin reductase-1 expression in astrocytomas of different grades. J Neurooncol 121 (3):451-458. doi:10.1007/s11060-014-1661-5
Yao A, Storr SJ, Al-Hadyan K, Rahman R, Smith S, Grundy R, Paine S, Martin SG (2020) Thioredoxin System Protein Expression Is Associated with Poor Clinical Outcome in Adult and Paediatric Gliomas and Medulloblastomas. Mol Neurobiol 57 (7):2889-2901. doi:10.1007/s12035-020-01928-z
Jovanovic M, Dragoj M, Zhukovsky D, Dar'in D, Krasavin M, Pesic M, Podolski-Renic A (2020) Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy. Front Mol Biosci 7. doi:10.3389/fmolb.2020.586146
Sally J, Helena B, Niina P, Timo J, Leo P, Hannu K, Pauli H, Vuokko K, Ylermi S, Hannu H (2006) Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival. J Neurooncol 77 (2):131-140. doi:10.1007/s11060-005-9030-z
Jia J-J, Geng W-S, Wang Z-Q, Chen L, Zeng X-S (2019) The role of thioredoxin system in cancer: strategy for cancer therapy. Cancer Chemother Pharmacol 84 (3):453-470. doi:10.1007/s00280-019-03869-4
Banerjee R (2012) Redox outside the Box: Linking Extracellular Redox Remodeling with Intracellular Redox Metabolism*. J Biol Chem 287 (7):4397-4402. doi:https://doi.org/10.1074/jbc.R111.287995
Nicolussi A, D'Inzeo S, Capalbo C, Giannini G, Coppa A (2017) The role of peroxiredoxins in cancer (Review). Mol Clin Oncol 6 (2):139-153. doi:10.3892/mco.2017.1129
Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, Lleonart ME (2013) Oxidative stress and cancer: An overview. Ageing Res Rev 12 (1):376-390. doi:https://doi.org/10.1016/j.arr.2012.10.004
de Lucca Camargo L, Touyz RM (2019) Reactive Oxygen Species. In: Touyz RM, Delles C (eds) Textbook of Vascular Medicine. Springer International Publishing, Cham, pp 127-136. doi:10.1007/978-3-030-16481-2_12
Tang J, Liu J, Lv S, Zhang K-b, Wang Y-l, Xu J (2016) PRDX-1 promotes cell proliferation and inhibits apoptosis of human gliomas via TNF-a/NF-kB pathway. Int J Clin Exp Pathol 9 (3):3152-3160
Cao J, Schulte J, Knight A, Leslie NR, Zagozdzon A, Bronson R, Manevich Y, Beeson C, Neumann CA (2009) Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. Embo j 28 (10):1505-1517. doi:10.1038/emboj.2009.101
Dittmann LM, Danner A, Gronych J, Wolter M, Stuhler K, Grzendowski M, Becker N, Bageritz J, Goidts V, Toedt G, Felsberg J, Sabel MC, Barbus S, Reifenberger G, Lichter P, Tews B (2012) Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro. Oncogene 31 (29):3409-3418. doi:10.1038/onc.2011.513
Koshkin PA, Chistiakov DA, Nikitin AG, Konovalov AN, Potapov AA, Usachev DY, Pitskhelauri DI, Kobyakov GL, Shishkina LV, Chekhonin VP (2014) Analysis of expression of microRNAs and genes involved in the control of key signaling mechanisms that support or inhibit development of brain tumors of different grades. Clin Chim Acta 430:55-62. doi:https://doi.org/10.1016/j.cca.2014.01.001
Su Y, Li X, Ji W, Sun B, Xu C, Li Z, Qian G, Su C (2014) Small molecule with big role: MicroRNAs in cancer metastatic microenvironments. Cancer Lett 344 (2):147-156. doi:10.1016/j.canlet.2013.10.024
Lema C, Cunningham MJ (2010) MicroRNAs and their implications in toxicological research. Toxicol Lett 198 (2):100-105. doi:https://doi.org/10.1016/j.toxlet.2010.06.019
Marumoto T, Saya H (2012) Molecular biology of glioma. Adv Exp Med Biol 746:2-11. doi:10.1007/978-1-4614-3146-6_1
Rao SAM, Santosh V, Somasundaram K (2010) Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. Mod Pathol 23 (10):1404-1417. doi:10.1038/modpathol.2010.135
Hu X, Chen D, Cui Y, Li Z, Huang J (2013) Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10. Sci Rep 3 (1):3423. doi:10.1038/srep03423
Zhi F, Zhou G, Wang S, Shi Y, Peng Y, Shao N, Guan W, Qu H, Zhang Y, Wang Q, Yang C, Wang R, Wu S, Xia X, Yang Y (2013) A microRNA expression signature predicts meningioma recurrence. Int J Cancer 132 (1):128-136. doi:10.1002/ijc.27658
Liu N, Zhang L, Wang Z, Cheng Y, Zhang P, Wang X, Wen W, Yang H, Liu H, Jin W, Zhang Y, Tu Y (2017) MicroRNA-101 inhibits proliferation, migration and invasion of human glioblastoma by targeting SOX9. Oncotarget 8 (12):19244-19254. doi:10.18632/oncotarget.13706
Mao J, Zhang M, Zhong M, Zhang Y, Lv K (2014) MicroRNA-204, a direct negative regulator of ezrin gene expression, inhibits glioma cell migration and invasion. Mol Cell Biochem 396 (1-2):117-128. doi:10.1007/s11010-014-2148-6
Wang Q, Li P, Li A, Jiang W, Wang H, Wang J, Xie K (2012) Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma. J Exp Clin Cancer Res 31 (1):97. doi:10.1186/1756-9966-31-97
Wu S, Lin Y, Xu D, Chen J, Shu M, Zhou Y, Zhu W, Su X, Zhou Y, Qiu P, Yan G (2012) MiR-135a functions as a selective killer of malignant glioma. Oncogene 31 (34):3866-3874. doi:10.1038/onc.2011.551
Paolini A, Curti V, Pasi F, Mazzini G, Nano R, Capelli E (2015) Gallic acid exerts a protective or an anti-proliferative effect on glioma T98G cells via dose-dependent epigenetic regulation mediated by miRNAs. Int J Oncol 46. doi:10.3892/ijo.2015.2864
Li KKW, Pang JCS, Lau KM, Zhou LF, Mao Y, Wang Y, Poon WS, Ng HK (2013) MiR-383 is Downregulated in Medulloblastoma and Targets Peroxiredoxin 3 (PRDX3). Brain Pathol 23 (4):413-425. doi:10.1111/bpa.12014
Yin F, Zhang JN, Wang SW, Zhou CH, Zhao MM, Fan WH, Fan M, Liu S (2015) MiR-125a-3p Regulates Glioma Apoptosis and Invasion by Regulating Nrg1. PLOS ONE 10 (1):e0116759. doi:10.1371/journal.pone.0116759
Zhao X, Xiao Z, Li B, Li H, Yang B, Li T, Mei Z (2021) miRNA-21 may serve as a promising noninvasive marker of glioma with a high diagnostic performance: a pooled analysis of 997 patients. Ther Adv Med Oncol 13:1758835920987650-1758835920987650. doi:10.1177/1758835920987650
Jiang G, Mu J, Liu X, Peng X, Zhong F, Yuan W, Deng F, Peng X, Peng S, Zeng X (2020) Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation. Sci Rep 10 (1):4220. doi:10.1038/s41598-020-61155-3
Qu K, Lin T, Pang Q, Liu T, Wang Z, Tai M, Meng F, Zhang J, Wan Y, Mao P, Dong X, Liu C, Niu W, Dong S (2016) Extracellular miRNA-21 as a novel biomarker in glioma: Evidence from meta-analysis, clinical validation and experimental investigations. Oncotarget 7 (23):33994-34010. doi:10.18632/oncotarget.9188
Ivo D'Urso P, Fernando D'Urso O, Damiano Gianfreda C, Mezzolla V, Storelli C, Marsigliante S (2015) miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma. Curr Genomics 16 (5):304-311. doi:10.2174/1389202916666150707155610
Hua S, Quan Y, Zhan M, Liao H, Li Y, Lu L (2019) miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1. Cancer Cell International 19 (1):203. doi:10.1186/s12935-019-0919-6
Knoll S, Fürst K, Kowtharapu B, Schmitz U, Marquardt S, Wolkenhauer O, Martin H, Pützer BM (2014) E2F1 induces miR-224/452 expression to drive EMT through TXNIP downregulation. EMBO Rep 15 (12):1315-1329. doi:10.15252/embr.201439392
Hopkins BL, Nadler M, Skoko JJ, Bertomeu T, Pelosi A, Shafaei PM, Levine K, Schempf A, Pennarun B, Yang B, Datta D, Bucur O, Ndebele K, Oesterreich S, Yang D, Giulia Rizzo M, Khosravi-Far R, Neumann CA (2018) A Peroxidase Peroxiredoxin 1-Specific Redox Regulation of the Novel FOXO3 microRNA Target let-7. Antioxidants & redox signaling 28 (1):62-77. doi:10.1089/ars.2016.6871
Chandimali N, Huynh DL, Zhang JJ, Lee JC, Yu D-Y, Jeong DK, Kwon T (2019) MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells. Cancer Gene Therapy 26 (9):292-304. doi:10.1038/s41417-018-0050-1
He H-c, Zhu J-g, Chen X-b, Chen S-m, Han Z-d, Dai Q-S, Ling X-H, Fu X, Lin Z-y, Deng Y-h, Qin G-Q, Cai C, Chen J-H, Zhong W-d (2012) MicroRNA-23b downregulates peroxiredoxin III in human prostate cancer. FEBS letters 586:2451-2458. doi:10.1016/j.febslet.2012.06.003
Zhu G, Zhou L, Liu H, Shan Y, Zhang X (2018) MicroRNA-224 Promotes Pancreatic Cancer Cell Proliferation and Migration by Targeting the TXNIP-Mediated HIF1α Pathway. Cell Physiol Biochem 48 (4):1735-1746. doi:10.1159/000492309
Degli Esposti D, Aushev VN, Lee E, Cros M-P, Zhu J, Herceg Z, Chen J, Hernandez-Vargas H (2017) miR-500a-5p regulates oxidative stress response genes in breast cancer and predicts cancer survival. Scientific Reports 7 (1):15966. doi:10.1038/s41598-017-16226-3
Jiang W, Min J, Sui X, Qian Y, Liu Y, Liu Z, Zhou H, Li X, Gong Y (2015) MicroRNA-26a-5p and microRNA-23b-3p up-regulate peroxiredoxin III in acute myeloid leukemia. Leukemia & Lymphoma 56 (2):460-471. doi:10.3109/10428194.2014.924115
Ciesielska S, Slezak-Prochazka I, Bil P, Rzeszowska-Wolny J (2021) Micro RNAs in Regulation of Cellular Redox Homeostasis. International Journal of Molecular Sciences 22 (11):6022
Lv Z, Wei J, You W, Wang R, Shang J, Xiong Y, Yang H, Yang X, Fu Z (2017) Disruption of the c-Myc/miR-200b-3p/PRDX2 regulatory loop enhances tumor metastasis and chemotherapeutic resistance in colorectal cancer. Journal of Translational Medicine 15 (1):257. doi:10.1186/s12967-017-1357-7
Zhang C, Shu L, Kong A-NT (2015) MicroRNAs: new Players in Cancer Prevention Targeting Nrf2, Oxidative Stress and Inflammatory Pathways. Current Pharmacology Reports 1 (1):21-30. doi:10.1007/s40495-014-0013-7
Guo QJ, Mills JN, Bandurraga SG, Nogueira LM, Mason NJ, Camp ER, Larue AC, Turner DP, Findlay VJ (2013) MicroRNA-510 promotes cell and tumor growth by targeting peroxiredoxin1 in breast cancer. Breast Cancer Research 15 (4):R70. doi:10.1186/bcr3464
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131 (6):803-820. doi:10.1007/s00401-016-1545-1
Ma F, Li W, Liu C, Li W, Yu H, Lei B, Ren Y, Li Z, Pang D, Qian C (2017) MiR-23a promotes TGF-β1-induced EMT and tumor metastasis in breast cancer cells by directly targeting CDH1 and activating Wnt/β-catenin signaling. Oncotarget 8 (41):69538-69550. doi:10.18632/oncotarget.18422
Gollapalli K, Ghantasala S, Atak A, Rapole S, Moiyadi A, Epari S, Srivastava S (2017) Tissue Proteome Analysis of Different Grades of Human Gliomas Provides Major Cues for Glioma Pathogenesis. Omics 21 (5):275-284. doi:10.1089/omi.2017.0028
Ren P, Ye H, Dai L, Liu M, Liu X, Chai Y, Shao Q, Li Y, Lei N, Peng B, Yao W, Zhang J (2013) Peroxiredoxin 1 is a tumor-associated antigen in esophageal squamous cell carcinoma. Oncol Rep 30 (5):2297-2303. doi:10.3892/or.2013.2714
Taniuchi K, Furihata M, Hanazaki K, Iwasaki S, Tanaka K, Shimizu T, Saito M, Saibara T (2015) Peroxiredoxin 1 promotes pancreatic cancer cell invasion by modulating p38 MAPK activity. Pancreas 44 (2):331-340. doi:10.1097/mpa.0000000000000270
Poschmann G, Grzendowski M, Stefanski A, Bruns E, Meyer HE, Stühler K (2015) Redox proteomics reveal stress responsive proteins linking peroxiredoxin-1 status in glioma to chemosensitivity and oxidative stress. Biochim Biophys Acta 1854 (6):624-631. doi:10.1016/j.bbapap.2014.11.011
Zheng M-J, Wang J, Wang H-M, Gao L-L, Li X, Zhang W-C, Gou R, Guo Q, Nie X, Liu J-J, Lin B (2018) Decreased expression of peroxiredoxin1 inhibits proliferation, invasion, and metastasis of ovarian cancer cell. Onco Targets Ther 11:7745-7761. doi:10.2147/OTT.S175009
Ding C, Fan X, Wu G (2017) Peroxiredoxin 1 - an antioxidant enzyme in cancer. J Cell Mol Med 21 (1):193-202. doi:10.1111/jcmm.12955
Wang Y, Liu M, Yang P, Peng H (2018) Peroxiredoxin 1 (PRDX1) Suppresses Progressions and Metastasis of Osteosarcoma and Fibrosarcoma of Bone. Med Sci Monit 24:4113-4120. doi:10.12659/MSM.908736
Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 Is an Antiapoptotic Factor in Human Glioblastoma Cells. Cancer Res 65 (14):6029-6033. doi:10.1158/0008-5472.Can-05-0137
Ross SA, Davis CD (2014) The emerging role of microRNAs and nutrition in modulating health and disease. Annu Rev Nutr 34:305-336. doi:10.1146/annurev-nutr-071813-105729
Bienertova-Vasku J, Sana J, Slaby O (2013) The role of microRNAs in mitochondria in cancer. Cancer Lett 336 (1):1-7. doi:https://doi.org/10.1016/j.canlet.2013.05.001
Chan B, Manley J, Lee J, Singh SR (2015) The emerging roles of microRNAs in cancer metabolism. Cancer Lett 356:301-308. doi:10.1016/j.canlet.2014.10.011
Diao H, Ye Z, Qin R (2018) miR-23a acts as an oncogene in pancreatic carcinoma by targeting FOXP2. J Investig Med 66 (3):676-683. doi:10.1136/jim-2017-000598
Khalighfard S, Alizadeh AM, Irani S, Omranipour R (2018) Plasma miR-21, miR-155, miR-10b, and Let-7a as the potential biomarkers for the monitoring of breast cancer patients. Sci Rep 8 (1):17981-17981. doi:10.1038/s41598-018-36321-3
Marques MM, Evangelista AF, Macedo T, Vieira RAdC, Scapulatempo-Neto C, Reis RM, Carvalho AL, Silva IDCGd (2018) Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer. Clinics 73:-. doi:10.6061/clinics/2018/e184
Sasayama T, Tanaka K, Kohmura E (2016) The Roles of MicroRNAs in Glioblastoma Biology and Biomarker. Neurooncol.
Bautista-Sánchez D, Arriaga-Canon C, Pedroza-Torres A, De La Rosa-Velázquez IA, González-Barrios R, Contreras-Espinosa L, Montiel-Manríquez R, Castro-Hernández C, Fragoso-Ontiveros V, Álvarez-Gómez RM, Herrera LA (2020) The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics. Mol Ther Nucleic Acids 20:409-420. doi:10.1016/j.omtn.2020.03.003
Kalinina EV, Ivanova-Radkevich VI, Chernov NN (2019) Role of MicroRNAs in the Regulation of Redox-Dependent Processes. Biochemistry (Mosc) 84 (11):1233-1246. doi:10.1134/s0006297919110026
Mercatelli N, Fittipaldi S, De Paola E, Dimauro I, Paronetto MP, Jackson MJ, Caporossi D (2017) MiR-23-TrxR1 as a novel molecular axis in skeletal muscle differentiation. Sci Rep 7 (1):7219-7219. doi:10.1038/s41598-017-07575-0

Download PDF

Version 1

posted 15 Oct, 2021

You are reading this latest preprint version

Tissue and Serum Thioredoxin System and miR-21, miR-23a/b and let-7a as Potential Biomarkers for Brain Tumor Progression

Status:

Version 1

Abstract

Figures

Introduction

Methods

Ethics Statement and Sample Collection

Quantitative Real-time Polymerase Chain Reaction (qRT-PCR)

Western blot

Enzyme-Linked ImmunoSorbent Assay (ELISA)

Statistical Analysis

Results

Thioredoxin system components showed higher mRNA expression but low protein expression in low-grade brain tumor tissues

Thioredoxin system components showed higher protein expression in serum samples of patients with low-grade brain tumors

miR-23a/b, miR-21 and let-7a are highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity

Discussion

Declarations

References

Status:

Version 1