Effect of aberrant DNA methylation on cancer stem cell properties

Mazloumi, Zeinab; Farahzadi, Raheleh; Rafat, Ali; Asl, Khadijeh Dizaji; Karimipour, Mohammad; Montazer, Majid; Movassaghpour, Ali Akbar; Dehnad, Alireza; Charoudeh, Hojjatollah Nozad

doi:10.1016/j.yexmp.2022.104757

Cited by 18 publications

(5 citation statements)

References 127 publications

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“…Similarly, the TAGLN2 DNA methylation landscape in pan-cancer was sketched. DNA methylation, as an epigenetic mechanism, occurs by adding a methyl group of cytosines in position 5 by DNA methyltransferases and abnormal methylation is well-known hallmark of cancer development and progression 23 . As illustrated by the lollipop chart in Figure 4 C , it reflected a significant correlation between TAGLN2 expression and methylation in a total of 30 tumors.…”

Section: Resultsmentioning

confidence: 99%

An Integrated Analysis Identified TAGLN2 As an Oncogene Indicator Related to Prognosis and Immunity in Pan-Cancer

Pan¹,

Wang²,

Wang³

2023

J. Cancer

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Background: Transgelin-2 (TAGLN2) has long been regarded as an actin-binding protein that modulates actin gelation and controls actin cytoskeleton dynamics. However, recent studies have reported that TAGLN2 can directly or indirectly participate in multiple cancer-related processes, including cell migration, proliferation, differentiation, and apoptosis. To further investigate the role of TAGLN2 in carcinogenesis, a comprehensive analysis was launched to evaluate the expression status and prognostic value of TAGLN2 in pan-cancer. Methods: Herein, data was retrieved from publicly online websites and databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), UCSC Xena, cBioPortal, Human Protein Atlas (HPA), TIMER2.0, CancerSEA, GDSC, and ImmuCellAI. Gene expression pattern and its correlation with prognosis were assessed across cancer types. Moreover, an analysis was conducted to explore the relationships between TAGLN2 and methylation, copy number values (CNVs), tumor microenvironment (TME), immune cell infiltration, immune-relevance genes, tumor mutation burden (TMB), microsatellite instability (MSI), and IC50. Additionally, R package “clusterProfiler” was utilized to perform enrichment analysis on TAGLN2. Finally, the ability of TAGLN2 as an oncogene was preliminarily verified in vitro in UCEC. Results: Our findings revealed that TAGLN2 was specifically overexpressed and related to an unfavorable prognosis in most cancers. There was a significant connection between TAGLN2 expression and methylation and CNVs. Besides, we identified TAGLN2 correlated to TME, immune cell infiltration, immune-relevant genes, TMB, and MSI, suggesting an immunoregulatory role in cancers. Notably, TAGLN2 expression showed a positive correlation with macrophages, and cancer-associated fibroblasts, whereas a negative correlation with the infiltration degree of B cells. Mechanically, the results obtained from Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) provided theory-supportive evidence that TAGLN2 interlinkages with immunity and programmed cell death. Overall, anti-tumor drugs were overtly associated with TAGLN2 dysregulation among diverse cancers. At last, UCEC cell lines with TAGLN2-depleting had an inhibition of the migration and invasion ability. Conclusions: These findings enriched the knowledge about the role of TAGLN2 in tumorigenesis and progression, revealing TAGLN2 may serve as a potential therapeutic strategy for various malignancies.

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Section: Resultsmentioning

confidence: 99%

An Integrated Analysis Identified TAGLN2 As an Oncogene Indicator Related to Prognosis and Immunity in Pan-Cancer

Pan¹,

Wang²,

Wang³

2023

J. Cancer

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“…50 Studies have shown that CSC formation can be caused by aberrant DNA methylation, which is a vital epigenetic abnormality. 51 DNMT1 overexpression correlates well with aberrant DNA methylation and is a characteristic change in solid cancers 16,52 (Fig. 3 and Table 1).…”

Section: Dnmt1 In Multiple Solid Cancersmentioning

confidence: 87%

“…50 Studies have shown that CSC formation can be caused by aberrant DNA methylation, which is a vital epigenetic abnormality. 51…”

Section: Dnmt1 and Various Cancers In Humansmentioning

confidence: 99%

A review on recent advances in assays for DNMT1: a promising diagnostic biomarker for multiple human cancers

Yu,

Fu,

Xie

et al. 2024

Analyst

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“…In breast cancer, the hypermethylation of the BRCA1 promoter has been associated with decreased BRCA1 expression and sensitivity to DNA‐damaging drugs and PARP inhibitors 207 . In contrast, the hypermethylation of the MLH1 promoter has been associated with decreased MLH1 expression and DNA repair capacity in cancer cells, which can increase the accumulation of somatic mutation in cancer cells and induce drug resistance 208 . These findings highlight the complex interplay among DNA methylation, DNA repair, and cancer resistance and suggest that targeting DNA methylation may be a promising strategy for overcoming drug resistance in cancer.…”

Section: Resistance Mechanisms In Cancer and Combating Strategiesmentioning

confidence: 99%

Understanding and targeting resistance mechanisms in cancer

Lei

Teng

Wurpel

et al. 2023

MedComm

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Resistance to cancer therapies has been a commonly observed phenomenon in clinical practice, which is one of the major causes of treatment failure and poor patient survival. The reduced responsiveness of cancer cells is a multifaceted phenomenon that can arise from genetic, epigenetic, and microenvironmental factors. Various mechanisms have been discovered and extensively studied, including drug inactivation, reduced intracellular drug accumulation by reduced uptake or increased efflux, drug target alteration, activation of compensatory pathways for cell survival, regulation of DNA repair and cell death, tumor plasticity, and the regulation from tumor microenvironments (TMEs). To overcome cancer resistance, a variety of strategies have been proposed, which are designed to enhance the effectiveness of cancer treatment or reduce drug resistance. These include identifying biomarkers that can predict drug response and resistance, identifying new targets, developing new targeted drugs, combination therapies targeting multiple signaling pathways, and modulating the TME. The present article focuses on the different mechanisms of drug resistance in cancer and the corresponding tackling approaches with recent updates. Perspectives on polytherapy targeting multiple resistance mechanisms, novel nanoparticle delivery systems, and advanced drug design tools for overcoming resistance are also reviewed.

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Effect of aberrant DNA methylation on cancer stem cell properties

Cited by 18 publications

References 127 publications

An Integrated Analysis Identified TAGLN2 As an Oncogene Indicator Related to Prognosis and Immunity in Pan-Cancer

An Integrated Analysis Identified TAGLN2 As an Oncogene Indicator Related to Prognosis and Immunity in Pan-Cancer

A review on recent advances in assays for DNMT1: a promising diagnostic biomarker for multiple human cancers

Understanding and targeting resistance mechanisms in cancer

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