Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival

Masiulionytė, Bernadeta; Valiulytė, Indrė; Tamašauskas, Arimantas; Skiriutė, Daina

doi:10.1038/s41598-019-41974-9

Cited by 20 publications

(25 citation statements)

References 26 publications

(30 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…MT gene expression has been associated with glioma malignancy grade, 7 and MT3 associates with a poor patient survival. 5 , 7 We have found that the GBM U87 cell line expresses high levels of MT3 mRNA, as compared to grade II 1321N1 astrocytoma cells. These differences are unlikely to depend on a different modulation of MT3 expression by intracellular labile zinc 36 because MT3 mRNA levels were not affected by zinc depletion and restoration.…”

Section: Discussionmentioning

confidence: 99%

“… 5 Interestingly, protein and mRNA profiling of MTs in different grade gliomas have suggested that MT expression correlates with the tumor grade and progression. 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

“… 10 , 11 More importantly, MT1A and MT2 gene expression have been found to be increased in glioblastoma specimens, as compared to grade I–III astrocytomas, and proposed as a marker for malignancy of astrocytic gliomas. 7 In addition, the MT content seems to be associated with resistance of different cancer types, including gliomas, to cytotoxic drugs. 12 − 15 Specifically, MT2A has been linked to chemoresistance in breast cancer 16 and osteosarcoma 17 cell lines, whereas MT3 has been associated with resistance to irradiation in both murine and human glioma cell lines.…”

Section: Introductionmentioning

confidence: 99%

“… 5 , 7 Masiulionytė and colleagues have suggested that MT3 gene could be used to prognosticate a patient’s survival. 7 In this context, MT3 may potentially activate transcription factors 21 or promote autophagy 18 , 22 by acting as a zinc donor and protect against oxidative stress because of its high cysteine content. 23 However, the data on the role of MT3 in carcinogenesis are not unequivocal.…”

Section: Introductionmentioning

confidence: 99%

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Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

2020

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Metallothioneins (MTs) are metal-binding proteins that are overexpressed in various human cancers and are thought to be associated with resistance to cytotoxic drugs. The knowledge on MT expression, regulation, and function in human gliomas is limited. We found that MT3 mRNA was highly expressed in cell lines derived from grade IV gliomas ( i.e ., A172 and U87 cells), as compared to grade II astrocytoma cells ( i.e ., 1321N1). Different from 1321N1, U87 cells were partly resistant to the alkylating drug, temozolomide (TMZ) (100 μM for 96 h), which induced a massive accumulation of U87 into the S and G2 fractions of the cell cycle but not apoptotic death. Silencing of MT3 did not significantly affect U87 cell proliferation and survival, but it delayed G1/S transition and favored the occurrence of apoptosis in TMZ-treated cells. Accordingly, the combination of MT3 silencing and TMZ treatment increased the protein levels of checkpoint kinase-1, which was ultimately responsible for the lasting G1 arrest and death of double treated U87 cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“… 5 Interestingly, protein and mRNA profiling of MTs in different grade gliomas have suggested that MT expression correlates with the tumor grade and progression. 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

2020

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Integrative analysis of immune‐related multi‐omics profiles identifies distinct prognosis and tumor microenvironment patterns in osteosarcoma

Shi

et al. 2022

Molecular Oncology

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Osteosarcoma (OS) is the most common primary malignancy of bone. Epigenetic regulation plays a pivotal role in cancer development in various aspects, including immune response. In this study, we studied the potential association of alterations in the DNA methylation and transcription of immune‐related genes with changes in the tumor microenvironment (TME) and tumor prognosis of OS. We obtained multi‐omics data for OS patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. By referring to curated immune signatures and using a consensus clustering method, we categorized patients based on immune‐related DNA methylation patterns (IMPs), and evaluated prognosis and TME characteristics of the resulting patient subgroups. Subsequently, we used a machine‐learning approach to construct an IMP‐associated prognostic risk model incorporating the expression of a six‐gene signature ( MYC , COL13A1 , UHRF2 , MT1A , ACTB , and GBP1 ), which was then validated in an independent patient cohort. Furthermore, we evaluated TME patterns, transcriptional variation in biological pathways, somatic copy number alteration, anticancer drug sensitivity, and potential responsiveness to immune checkpoint inhibitor therapy with regard to our IMP‐associated signature scoring model. By integrative IMP and transcriptomic analysis, we uncovered distinct prognosis and TME patterns in OS. Finally, we constructed a classifying model, which may aid in prognosis prediction and provide a potential rationale for targeted‐ and immune checkpoint inhibitor therapy in OS.

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Metallothionein isoforms as double agents – Their roles in carcinogenesis, cancer progression and chemoresistance

Rodrigo

Jimemez

Haddad

et al. 2020

Drug Resistance Updates

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Metallothioneins (MTs) are small cysteine-rich intracellular proteins with four major isoforms identified in mammals, designated MT-1 through MT-4. The best-known biological functions of MTs are their ability to bind and sequester metal ions and their active role in redox homeostasis. Despite these protective roles, numerous studies have demonstrated that changes in MT expression could be associated with the process of carcinogenesis and participation in cell differentiation, proliferation, migration, and angiogenesis. Hence, MTs have the role of double agents, i.e., working with and against cancer. In view of their rich biochemical properties, it is not surprising that MTs participate in the emergence of chemoresistance in tumor cells. Many studies have demonstrated that MT overexpression is involved in the acquisition of resistance to anticancer drugs, including cisplatin, anthracyclines, tyrosine kinase inhibitors and mitomycin. The evidence is slowly becoming available for a cellular switch in MT functions, showing that they indeed have two faces: protector and saboteur.Initially, MTs display anti-oncogenic and protective roles; however, once the oncogenetic process has started, MTs are utilized by cancer cells for progression, survival, and the coordination of chemoresistance. The duality of MTs can serve as a potential prognostic/diagnostic biomarker and can therefore open the door to new strategies in cancer treatment. Herein, we review and discuss MTs as tumor disease markers and describe their role in chemoresistance to distinct anticancer drugs.

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Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival

Cited by 20 publications

References 26 publications

Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide

Integrative analysis of immune‐related multi‐omics profiles identifies distinct prognosis and tumor microenvironment patterns in osteosarcoma

Metallothionein isoforms as double agents – Their roles in carcinogenesis, cancer progression and chemoresistance

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