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001-es BibID:BIBFORM103405
035-os BibID:(cikkazonosító)2060 (WoS)000858038100001 (Scopus)85138606448
Első szerző:Beke-Varga Alexandra Edit (molekuláris biológus)
Cím:Suppressing the PI3K/AKT Pathway by miR-30d-5p Mimic Sensitizes Ovarian Cancer Cells to Cell Death Induced by High-Dose Estrogen / Varga Alexandra, Márton Éva, Markovics Arnold, Penyige András, Balogh István, Nagy Bálint, Szilágyi Melinda
Dátum:2022
ISSN:2227-9059
Megjegyzések:MicroRNAs are short non-coding RNA molecules that are involved in tumor development and are considered to be promising candidates in cancer therapy. Here, we studied the role of miR-30s in the pathophysiology of ovarian cancer. According to our results miR-30a-5p, miR-30d-5p, and miR-30e-5p were overexpressed in the estrogen receptor alpha (ER alpha)-expressing PEO1 cell line compared to A2780 that lacks this receptor. Furthermore, the expression of miR-30a-5p, miR-30d-5p, and miR-30e-5p were induced in response to high-dose estrogen treatment in PEO1 where intensive cell death was observed according to the induction of apoptosis and autophagy. Lacking or blocking ER alpha function reduced tolerance to high-dose estrogen that suggests the importance of ER alpha-mediated estrogen response in the maintenance of proliferation. MiR-30d-5p mimic reduced cell proliferation in both A2780 and PEO1. Furthermore, it decreased the tolerance of PEO1 cells to high-dose estrogen by blocking the ER alpha-mediated estrogen response. This was accompanied by decreased SOX4 expression that is thought to be involved in the regulation of the PI3K/AKT pathway. Blocking this pathway by AZD8835 led to the same results. MiR-30d-5p or AZD8835 sensitized PEO1 cells to tamoxifen. We suggest that miR-30d-5p might be a promising candidate in the therapy of ovarian cancer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
miR-30
ovarian cancer
estrogen receptor
high-dose estrogen
cell proliferation
cell death
sox4
PI3K/AKT
cancer therapy
tamoxifen
Megjelenés:Biomedicines. - 10 : 9 (2022), p. 1-19. -
További szerzők:Márton Éva (1992-) (biológus) Markovics Arnold (1988-) (molekuláris biológus) Penyige András (1954-) (molekuláris genetikus) Balogh István (1972-) (molekuláris biológus, genetikus) Nagy Bálint (1956-) (molekuláris genetikus) Szilágyi Melinda (1984-) (biológus)
Pályázati támogatás:EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
138021
OTKA
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM108635
035-os BibID:(cikkazonosító)140 (Scopus)85148964475
Első szerző:Márton Éva (biológus)
Cím:Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells / Éva Márton, Alexandra Varga, András Penyige, Zsuzsanna Birkó, István Balogh, Bálint Nagy, Melinda Szilágyi
Dátum:2023
ISSN:2072-6651
Megjegyzések:Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log2FC > 1); 292, 260 and 45 genes were downregulated (log2FC < ?1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log2FC > 1, or log2FC < ?1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501- 5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
xenoösztrogén
zearalenon
mikotoxin
biszfenol A
petefészekrák
transzkriptomika
mikroRNS
RNS szekvenálás
Megjelenés:Toxins. - 15 : 2 (2023), p. 1-22. -
További szerzők:Beke-Varga Alexandra Edit (1994-) (molekuláris biológus) Penyige András (1954-) (molekuláris genetikus) Hádáné Birkó Zsuzsanna (1971-) (molekuláris genetikus) Balogh István (1972-) (molekuláris biológus, genetikus) Nagy Bálint (1956-) (molekuláris genetikus) Szilágyi Melinda (1984-) (biológus)
Pályázati támogatás:FK138021
OTKA
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM091613
035-os BibID:(WoS)000632094300001 (Scopus)85101520969
Első szerző:Márton Éva (biológus)
Cím:Comparative Analysis of Cell-Free miR-205-5p, let-7f-5p, and miR-483-5p Expression in Ovarian Cell Cultures and Plasma Samples of Patients with Ovarian Cancer / Éva Márton, Alexandra Varga, Beáta Soltész, András Penyige, János Lukács, Róbert Póka, Bálint Nagy, Melinda Szilágyi
Dátum:2021
Megjegyzések:The term liquid biopsy reveals a non-invasive diagnostic method that might be based on the quantification of cell-free microRNAs in body fluids. However, the identification of candidates for liquid biopsy is challenging. Our aim was to compare the cell-free expression of miR-483-5p, miR-205-5p, and let-7f-5p in ovarian cell cultures and plasma samples of patients with ovarian cancer. Both the intracellular and cell-free expression of miR-205-5p and let-7f-5p proved to be higher in the Estrogen Receptor ? (ER?) expressing PEO1 cell-line than in the estrogen non-sensitive A2780. Moreover, the expression of let-7f-5p was up-regulated in response to estradiol exposure that was diminished after the addition of an ER? selective antagonist. MiR-483-5p had lower intracellular and cell-free expression in PEO1. All these miRNAs had detectable expression level in plasma samples, among which miR-205-5p proved to be overexpressed in the plasma samples of patients with ovarian tumors compared to healthy controls and possessed an acceptable diagnostic potential with ROC-AUC 0.683 (95% CI 0.57?0.795). Functional annotation clustering of the target genes of miR-205-5p revealed several clusters involved in cancer development. We suggest that miR-205-5p might be a promising biomarker candidate in ovarian cancer that should be further analyzed in larger sample size.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
microRNA
ovarian cancer
liquid biopsy
Megjelenés:Applied Sciences-Basel. - 11 : 4 (2021), p. 1-10. -
További szerzők:Beke-Varga Alexandra Edit (1994-) (molekuláris biológus) Soltész Beáta (1987-) (molekuláris biológus) Penyige András (1954-) (molekuláris genetikus) Lukács János (1975-) (szülész-nőgyógyász, genetikus) Póka Róbert (1960-) (szülész-nőgyógyász, klinikai onkológus) Nagy Bálint (1956-) (molekuláris genetikus) Szilágyi Melinda (1984-) (biológus)
Pályázati támogatás:ÚNKP-20-3
Egyéb
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM090169
035-os BibID:(cikkazonosító)9725 (scopus)85098209070 (wos)000603503300001
Első szerző:Márton Éva (biológus)
Cím:The Cell-Free Expression of MiR200 Family Members Correlates with Estrogen Sensitivity in Human Epithelial Ovarian Cells / Éva Márton, Alexandra Varga, Lajos Széles, Lóránd Göczi, András Penyige, Bálint Nagy, Melinda Szilágyi
Dátum:2020
ISSN:1661-6596 1422-0067
Megjegyzések:Exposure to physiological estrogens or xenoestrogens (e.g., zearalenone or bisphenol A) increases the risk for cancer. However, little information is available on their significance in ovarian cancer. We present a comprehensive study on the effect of estradiol, zearalenone and bisphenol A on the phenotype, mRNA, intracellular and cell-free miRNA expression of human epithelial ovarian cell lines. Estrogens induced a comparable effect on the rate of cell proliferation and migration as well as on the expression of estrogen-responsive genes (GREB1, CA12, DEPTOR, RBBP8) in the estrogen receptor ? (ER?)-expressing PEO1 cell line, which was not observable in the absence of this receptor (in A2780 cells). The basal intracellular and cell-free expression of miR200s and miR203a was higher in PEO1, which was accompanied with low ZEB1 and high E-cadherin expression. These miRNAs showed a rapid but intermittent upregulation in response to estrogens that was diminished by an ER?-specific antagonist. The role of ER? in the regulation of the MIR200B-MIR200A-MIR429 locus was further supported by publicly available ChIP-seq data. MiRNA expression of cell lysates correlated well with cell-free miRNA expression. We conclude that cell-free miR200s might be promising biomarkers to assess estrogen sensitivity of ovarian cells.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ovarian cancer
estrogen
zeralenone
bisphenol
estrogen receptor
cell-free miRNA
miR200
miR203a
EMT
Megjelenés:International Journal of Molecular Sciences. - 21 : 24 (2020), p. 1-19. -
További szerzők:Beke-Varga Alexandra Edit (1994-) (molekuláris biológus) Széles Lajos (1971-) (molekuláris biológus) Göczi Loránd (informatikus) Penyige András (1954-) (molekuláris genetikus) Nagy Bálint (1956-) (molekuláris genetikus) Szilágyi Melinda (1984-) (biológus)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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