Telomere-associated genes and telomeric lncRNAs are biomarker candidates in lung squamous cell carcinoma (LUSC)

Storti, Camila Baldin; Oliveira, Rogério Antônio de; Carvalho, Marcelo; Hasimoto, Érica Nishida; Catâneo, Daniele Cristina; Catâneo, Antônio José Maria; Faveri, Júlio De; Vasconcelos, Elton J R; Reis, Patrícia P.; Cano, Maria Isabel Nogueira

doi:10.1016/j.yexmp.2019.104354

Cited by 20 publications

(18 citation statements)

References 94 publications

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“…The abnormal expression of lncRNAs is closely associated with the tumorgenesis and progression of NSCLC, and lncRNAs may be potentially efficient biomarkers for early diagnosis and therapy of NSCLC. 18,19 The primary results of the present study provide new insights into the modulatory role of WT1-AS/miR-494-3p in NSCLC progression via PTEN/PI3K/AKT pathway. Considerable evidence has shown that WT1-AS is associated with the progression of several types of tumors through regulating cell proliferation and metastasis.…”

Section: Discussionmentioning

confidence: 79%

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

Wu¹,

Yang²,

Li³

et al. 2021

OTT

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Background Non-small cell lung cancer (NSCLC) is one of the most common malignancies with the highest morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) are recently recognized as noteworthy regulators of different tumors, counting NSCLC. However, the biological functions and regulatory mechanism of lncRNA WT1-AS in NSCLC progression still stay uninvestigated. Methods WT1-AS and miR-494-3p levels in NSCLC cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). In the current study, the regulatory effects of WT1-AS/miR-494-3p axis on cellular behaviors of NSCLC cell lines (A549 and NCI-H1975) were evaluated by a variety of methods. Cell counting kit-8 (CCK-8) and EDU assays were adopted to assess NSCLC cell proliferation. Tunnel staining and flow cytometry assay were applied to determine cell apoptosis and cell cycle distribution. Besides, cell migration and invasion abilities were analyzed by performing wound healing and transwell assays. Meanwhile, the levels of key proteins related to NSCLC cell apoptosis and PTEN/PI3K/AKT pathway were examined using Western blot assay. In addition, luciferase reporter assays were used to determine the interaction between WT1-AS and miR-494-3p or miR-494-3p and PTEN. Results Visibly downregulated WT1-AS in NSCLC cell lines was obtained from Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and further verified by performing RT-qPCR. Besides, miR-494-3p was the downstream target gene of WT1-AS and obviously upregulated miR-494-3p in NSCLC cell lines was confirmed. WT1-AS overexpression suppressed cell proliferation, migration and invasion abilities while enhanced cell apoptosis of A549 and NCI-H1975 cells. Furthermore, upregulation of miR-494-3p distinctly reversed these inhibitory effects of WT1-AS overexpression on the tumorigenesis and progression of NSCLC. In addition, WT1-AS promoted PTEN expression and thereby inhibited activation of PI3K/AKT pathway by sponging miR-494-3p. Conclusion To conclude, lncRNA WT1-AS impeded cell proliferation, migration, invasion but accelerated cell apoptosis via negatively regulating miR-494-3p to mediate PTEN/PI3K/AKT pathway in NSCLC.

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Section: Discussionmentioning

confidence: 79%

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

Wu¹,

Yang²,

Li³

et al. 2021

OTT

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“…Sci. 2020, 21, 2838 2 of 24 participate in the regulation of telomere function [7,8] and have been proposed as prognostic markers in different types of tumors [9][10][11]. Therefore, telomeres together with telomerase, shelterin proteins and TERRA play crucial roles in the maintenance of genome integrity and stability.…”

Section: Introductionmentioning

confidence: 99%

Insertion of Telomeric Repeats in the Human and Horse Genomes: An Evolutionary Perspective

Santagostino

Piras

Cappelletti

et al. 2020

IJMS

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Interstitial telomeric sequences (ITSs) are short stretches of telomeric-like repeats (TTAGGG)n at nonterminal chromosomal sites. We previously demonstrated that, in the genomes of primates and rodents, ITSs were inserted during the repair of DNA double-strand breaks. These conclusions were derived from sequence comparisons of ITS-containing loci and ITS-less orthologous loci in different species. To our knowledge, insertion polymorphism of ITSs, i.e., the presence of an ITS-containing allele and an ITS-less allele in the same species, has not been described. In this work, we carried out a genome-wide analysis of 2504 human genomic sequences retrieved from the 1000 Genomes Project and a PCR-based analysis of 209 human DNA samples. In spite of the large number of individual genomes analyzed we did not find any evidence of insertion polymorphism in the human population. On the contrary, the analysis of ITS loci in the genome of a single horse individual, the reference genome, allowed us to identify five heterozygous ITS loci, suggesting that insertion polymorphism of ITSs is an important source of genetic variability in this species. Finally, following a comparative sequence analysis of horse ITSs and of their orthologous empty loci in other Perissodactyla, we propose models for the mechanism of ITS insertion during the evolution of this order.

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“…First, we assessed differentially expressed TRGs (NDMM subgroups vs. control), which are involved in a multitude of intrinsic biological pathways including helicase, telomerase, shelterin-complex, DNA-repair, or related biosynthetic activities, as summarized elsewhere [ 29 ]. Differential expression of epigenetically regulated TRGs have also been reported in relation to their importance to the development of different types of cancer [ 34 , 35 ]. We aimed to evaluate the impact of 70 known TRGs in MM and observed a subgroup-specific differential expression pattern among the NDMM subgroups.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients

Choudhury

Ashby

Zhan

et al. 2021

Cancers

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High-risk Multiple Myeloma (MM) patients were found to maintain telomere length (TL), below the margin of short critical length, consistent with proactive overexpression of telomerase. Previously, DNA methylation has been shown as a determinant of telomere-related gene (TRG) expression and TL to assess risk in different types of cancer. We mapped genome-wide DNA methylation in a cohort of newly diagnosed MM (NDMM; n = 53) patients of major molecular subgroups, compared to age-matched healthy donors (n = 4). Differential methylation and expression at TRG-loci were analyzed in combination with overlapping chromatin marks and underlying DNA-sequences. We observed a strong correlation (R2 ≥ 0.5) between DNA methylation and expression amongst selective TRGs, such that demethylation at the promoters of DDX1 and TERF1 were associated to their oncogenic upregulation, while demethylation at the bodies of two key tumor suppressors ZNF208 and RAP1A led to downregulation of the genes. We demonstrated that TRG expression may be controlled by DNA methylation alone or in cooperation with chromatin modifications or CCCTC-binding factor at the regulatory regions. Additionally, we showed that hypomethylated DMRs of TRGs in NDMM are stabilized with G-quadruplex forming sequences, suggesting a crucial role of these epigenetically vulnerable loci in MM pathogenesis. We have identified a panel of five TRGs, which are epigenetically deregulated in NDMM patients and may serve as early detection biomarkers or therapeutic targets in the disease.

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Telomere-associated genes and telomeric lncRNAs are biomarker candidates in lung squamous cell carcinoma (LUSC)

Cited by 20 publications

References 94 publications

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer

Insertion of Telomeric Repeats in the Human and Horse Genomes: An Evolutionary Perspective

Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients

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