Locus-Specific Methylation of GSTP1, RNF219, and KIAA1539 Genes with Single Molecule Resolution in Cell-Free DNA from Healthy Donors and Prostate Tumor Patients: Application in Diagnostics

Bryzgunova, Olga E.; Bondar, Anna; Ruzankin, Pavel; Laktionov, Petr P.; Tarasenko, Anton; Kurilshikov, Alexander; Epifanov, Rostislav; Zaripov, M. M.; Kabilov, Мarsel R.; Laktionov, Pavel P.

doi:10.3390/cancers13246234

Cited by 9 publications

(9 citation statements)

References 71 publications

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“…However, the authors have also shown that cfDNA methylation analysis alone is not sufficient for successful cancer detection. The reasons for the decrease in the effectiveness of PCR may be the methylation mode, when not all CpG dinucleotides in the promoter region are simultaneously methylated [ 37 ], as well as allele-specific methylation [ 43 ]. At the same time, some new approaches, such as the use of NGS sequencing targeting a specific locus make it possible to overcome such limitations [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…The reasons for the decrease in the effectiveness of PCR may be the methylation mode, when not all CpG dinucleotides in the promoter region are simultaneously methylated [ 37 ], as well as allele-specific methylation [ 43 ]. At the same time, some new approaches, such as the use of NGS sequencing targeting a specific locus make it possible to overcome such limitations [ 43 ]. It should be mentioned that the low level of aberrantly methylated DNA in cfDNA represents a serious limitation in all methods aimed at analyzing tumor DNA circulating in the blood.…”

Section: Discussionmentioning

confidence: 99%

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Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Тамкович

Tupikin

Kozyakov³

et al. 2022

IJMS

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Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown to bind with the blood cell surface, we studied the concentration, representation, and fragmentation of tumor-derived methylated DNA in cell-free and cell-surface-associated DNA. We found that long DNA fragments (more than 10 kb) are mainly associated with the surface of blood cells. However, in plasma short DNA fragments (100–1000 bp) were also found along with long DNA fragments. Isolation of short fragments after separation of cirDNA in 6% PAGE followed by quantitative PCR (L1 element) has shown that short DNA fragments in healthy females represent 22% versus 0.5–4.4% in breast cancer patients. The methylated form of the RARβ2 gene was detected only in long DNA fragments by Real-time TaqMan PCR of bisulfite-converted DNA. The methylation index of cirDNA from healthy women was estimated at 0%, 9%, and 7% in plasma, PBS-EDTA, and trypsin eluates from the surface of blood cells, respectively. The methylation index of breast cancer patients’ DNA was found to be 33%, 15%, and 61% in the same fractions confirming the overrepresentation of methylated DNA in csbDNA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Тамкович

Tupikin

Kozyakov³

et al. 2022

IJMS

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“…Importantly, circGNB1 overexpression increased OA severity in the DMM mouse model, whereas circGNB1 silencing had the opposite effect. RNF219 (also known as C13orf7) plays a role in prostate tumors, 47 attention-deficit/hyperactivity disorder 48 and other diseases, 49 although its role in OA remains unclear. In this article, our results indicated that RNF219 expression was up-regulated in the cartilage of the medial tibial plateaus in older patients.…”

Section: Discussionmentioning

confidence: 99%

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes

Liang

Shen

et al. 2023

Clinical & Translational Med

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BackgroundCircular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age‐related osteoarthritis (OA).MethodsThe relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain‐ and loss‐of‐function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model.ResultsIncreased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR‐152‐3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin‐1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL‐10 signalling by antagonizing miR‐152‐3p‐mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA.ConclusionCircGNB1 regulated oxidative stress and OA progression via the miR‐152‐3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.

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“…In our study it is blood and semen. Blood is commonly used in diagnostics but low in cfDNA concentration while semen is, partly, secreted from the prostate, and high in cfDNA concentrations [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…In our study, it is blood and semen. Blood is commonly used in diagnostics but low in cfDNA concentration while semen is, partly, secreted from the prostate and high in cfDNA concentrations [ 21 , 22 ]. Considering the variety of genetic alternations in PCa (113 mutations in 72 driver gene loci), we focused on epigenetic modifications which are restricted to promoters and retain specific patterns within the same cancer model [ 23–25 ].…”

Section: Discussionmentioning

confidence: 99%

Methylation pattern of Caveolin-1 in prostate cancer as potential cfDNA biomarker

Škara

Vodopić

Pezelj³

et al. 2022

Bosn J of Basic Med Sci

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High prevalence and mortality of prostate cancer (PCa) are well known global health issues. Novel biomarkers for better identifying patients with PCa are the subject of extensive research. Prostate specific antigen (PSA) shows low specificity in screening and diagnostics, leading to unnecessary biopsies and health costs. Eighty patients with PCa and benign prostate hyperplasia (BPH) were included in the study. We analyzed CAV1 gene expression and methylation in tissue. CAV1 cfDNA methylation from blood and seminal plasma was accessed as a potential PCa biomarker. Although methylation in blood plasma did not differ between PCa and BPH patients, methylation in seminal plasma showed better PCa biomarker performances than tPSA (AUC 0.63 vs. AUC 0.52). Discrimination of BPH and Gleason grade group 1 PCa patients from patients with higher Gleason grade groups revealed very good performance as well (AUC 0.72). CAV1 methylation is useful biomarker with potential for further seminal plasma cfDNA research, but its diagnostic accuracy should be improved, as well as general knowledge about cfDNA in seminal plasma.

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Locus-Specific Methylation of GSTP1, RNF219, and KIAA1539 Genes with Single Molecule Resolution in Cell-Free DNA from Healthy Donors and Prostate Tumor Patients: Application in Diagnostics

Cited by 9 publications

References 71 publications

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes

Methylation pattern of Caveolin-1 in prostate cancer as potential cfDNA biomarker

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