TY  - JOUR
AU  - Petrović, Nina
AU  - Ergün, Sercan
AU  - Đorđić-Crnogorac, Marija
AU  - Stanojković, Tatjana
AU  - Mališić, Emina
AU  - Matić Ivana Z.
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10706
AB  - Phytochemicals and bioactive substances derived from a wide range of plant extracts have been reported to exert various anticancer effects. Prostate cancer is one of the leading causes of cancer-related deaths within the male population. Prostate cancer-specific miRNA signatures were associated with cancer formation and progression, with various subtypes, and response to therapy. MicroRNA levels of expression were shown to change after the treatment of various compounds and substances extracted from natural products. Natural herbal compounds were shown to induce variations in miRNA expression levels in cancer cells. The aims of this study were to investigate the cytotoxic effects of methanol, ethyl-acetate, and hexane extracts obtained from branch-body part and flowers of Hypericum perforatum L. against humane PC-3 and DU 145 and to test potential miRNA-128/133b/155/193a/206/21/335 signature changes and differences between the two prostate cancer cell lines. Cytotoxic activity of H. perforatum extracts, their effects on cell cycle distribution, and miRNA expression levels were examined in humane PC-3 and DU 145 prostate cancer cells by MTT cell survival assay, flow cytometry, and quantitative real-time PCR. Hexane extract of flowers showed the strongest intensity of cytotoxic activity against PC-3 and DU 145 cells. The highest increase in the percentage of PC-3 cells in the subG1 phase was observed in cell samples treated with hexane extract of flowers and branch-body part. Significant differences in miRNA-128/133b/155/193a/206/21/335 levels were observed between PC-3 and DU 145 cell lines, especially in samples treated with flower extracts compared with the branch-body part. Conclusions: Investigated extracts have significant anticancer potential not only from the aspects of cytotoxicity and cell cycle effects but also from the aspect of lowering oncogenic or increasing tumor-suppressive miRNAs. The best effect might be the increase of tumor-suppressive miR-128 (accompanied by miR-193a) induced by the hexane extract of the flowers, which also exerted the highest cytotoxic activity. Hexane extract of flowers may be the candidate for further investigation for improving the efficiency of standard therapies for PCa. A miRNA signature might be cell-type specific after the treatment with H. perforatum extracts.
T2  - Genetika
T1  - Hypericum perforatum L. extracts exert cytotoxic effects and show different miRNA signatures in PC-3 and DU 145 prostate cancer cells
VL  - 54
IS  - 3
SP  - 1249
EP  - 1270
DO  - 10.2298/GENSR2203249P
ER  - 

@article{
author = "Petrović, Nina and Ergün, Sercan and Đorđić-Crnogorac, Marija and Stanojković, Tatjana and Mališić, Emina and Matić Ivana Z.",
year = "2022",
abstract = "Phytochemicals and bioactive substances derived from a wide range of plant extracts have been reported to exert various anticancer effects. Prostate cancer is one of the leading causes of cancer-related deaths within the male population. Prostate cancer-specific miRNA signatures were associated with cancer formation and progression, with various subtypes, and response to therapy. MicroRNA levels of expression were shown to change after the treatment of various compounds and substances extracted from natural products. Natural herbal compounds were shown to induce variations in miRNA expression levels in cancer cells. The aims of this study were to investigate the cytotoxic effects of methanol, ethyl-acetate, and hexane extracts obtained from branch-body part and flowers of Hypericum perforatum L. against humane PC-3 and DU 145 and to test potential miRNA-128/133b/155/193a/206/21/335 signature changes and differences between the two prostate cancer cell lines. Cytotoxic activity of H. perforatum extracts, their effects on cell cycle distribution, and miRNA expression levels were examined in humane PC-3 and DU 145 prostate cancer cells by MTT cell survival assay, flow cytometry, and quantitative real-time PCR. Hexane extract of flowers showed the strongest intensity of cytotoxic activity against PC-3 and DU 145 cells. The highest increase in the percentage of PC-3 cells in the subG1 phase was observed in cell samples treated with hexane extract of flowers and branch-body part. Significant differences in miRNA-128/133b/155/193a/206/21/335 levels were observed between PC-3 and DU 145 cell lines, especially in samples treated with flower extracts compared with the branch-body part. Conclusions: Investigated extracts have significant anticancer potential not only from the aspects of cytotoxicity and cell cycle effects but also from the aspect of lowering oncogenic or increasing tumor-suppressive miRNAs. The best effect might be the increase of tumor-suppressive miR-128 (accompanied by miR-193a) induced by the hexane extract of the flowers, which also exerted the highest cytotoxic activity. Hexane extract of flowers may be the candidate for further investigation for improving the efficiency of standard therapies for PCa. A miRNA signature might be cell-type specific after the treatment with H. perforatum extracts.",
journal = "Genetika",
title = "Hypericum perforatum L. extracts exert cytotoxic effects and show different miRNA signatures in PC-3 and DU 145 prostate cancer cells",
volume = "54",
number = "3",
pages = "1249-1270",
doi = "10.2298/GENSR2203249P"
}

Petrović, N., Ergün, S., Đorđić-Crnogorac, M., Stanojković, T., Mališić, E.,& Matić Ivana Z.. (2022). Hypericum perforatum L. extracts exert cytotoxic effects and show different miRNA signatures in PC-3 and DU 145 prostate cancer cells. in Genetika, 54(3), 1249-1270.
https://doi.org/10.2298/GENSR2203249P

Petrović N, Ergün S, Đorđić-Crnogorac M, Stanojković T, Mališić E, Matić Ivana Z.. Hypericum perforatum L. extracts exert cytotoxic effects and show different miRNA signatures in PC-3 and DU 145 prostate cancer cells. in Genetika. 2022;54(3):1249-1270.
doi:10.2298/GENSR2203249P .

Petrović, Nina, Ergün, Sercan, Đorđić-Crnogorac, Marija, Stanojković, Tatjana, Mališić, Emina, Matić Ivana Z., "Hypericum perforatum L. extracts exert cytotoxic effects and show different miRNA signatures in PC-3 and DU 145 prostate cancer cells" in Genetika, 54, no. 3 (2022):1249-1270,
https://doi.org/10.2298/GENSR2203249P . .

TY  - JOUR
AU  - Matić, Ivana Z.
AU  - Ergün, Sercan
AU  - Đorđić Crnogorac, Marija
AU  - Misir, Sema
AU  - Aliyazicioğlu, Yüksel
AU  - Damjanović, Ana
AU  - Džudžević-Čančar, Hurija
AU  - Stanojković, Tatjana P.
AU  - Konanç, Kalbiye
AU  - Petrović, Nina
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9406
AB  - Six extracts were obtained from plant species Hypericum perforatum L., collected at Samsun in Turkey. The aim of this study was to examine the mechanisms of the anticancer activity of these extracts. Methanol, ethyl-acetate and hexane were used as a solvents for extraction from both branch-body part of the plant (extracts 1, 2 and 3) and from plant flowers (extracts 4, 5 and 6). The cytotoxic effects of the extracts were determined against 2D and 3D cancer cell models. Cell cycle changes of treated HeLa cells were analyzed by flow cytometry. Measurements of gene and microRNA expression levels in treated HeLa cells were done by quantitative real time PCR. Five examined extracts (2–6) exerted selective concentration-dependent cytotoxic effects on HeLa, K562, and A549 cancer cells, while the extract 1 exhibited very weak cytotoxicity. The extract 6 showed the highest intensity of cytotoxic activity. All tested extracts (2–6) demonstrated the ability to induce apoptosis in HeLa cells through activation of caspase-3. These extracts remarkably decreased gene expression levels of MMP2, MMP9, TIMP3, and VEGFA in HeLa cells. Flower extracts might have stronger effects on miR128/193a-5p/335 level changes than branch-body extracts. Hypericum perforatum extracts exerted weaker cytotoxic effects on 3D HeLa spheroids when compared with their effects on 2D monolayer HeLa cells. Taken together, results of our research may suggest the promising anticancer properties of the Hypericum perforatum extracts. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
T2  - Cytotechnology
T1  - Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models
VL  - 73
IS  - 3
SP  - 373
EP  - 389
DO  - 10.1007/s10616-021-00464-5
ER  - 

@article{
author = "Matić, Ivana Z. and Ergün, Sercan and Đorđić Crnogorac, Marija and Misir, Sema and Aliyazicioğlu, Yüksel and Damjanović, Ana and Džudžević-Čančar, Hurija and Stanojković, Tatjana P. and Konanç, Kalbiye and Petrović, Nina",
year = "2021",
abstract = "Six extracts were obtained from plant species Hypericum perforatum L., collected at Samsun in Turkey. The aim of this study was to examine the mechanisms of the anticancer activity of these extracts. Methanol, ethyl-acetate and hexane were used as a solvents for extraction from both branch-body part of the plant (extracts 1, 2 and 3) and from plant flowers (extracts 4, 5 and 6). The cytotoxic effects of the extracts were determined against 2D and 3D cancer cell models. Cell cycle changes of treated HeLa cells were analyzed by flow cytometry. Measurements of gene and microRNA expression levels in treated HeLa cells were done by quantitative real time PCR. Five examined extracts (2–6) exerted selective concentration-dependent cytotoxic effects on HeLa, K562, and A549 cancer cells, while the extract 1 exhibited very weak cytotoxicity. The extract 6 showed the highest intensity of cytotoxic activity. All tested extracts (2–6) demonstrated the ability to induce apoptosis in HeLa cells through activation of caspase-3. These extracts remarkably decreased gene expression levels of MMP2, MMP9, TIMP3, and VEGFA in HeLa cells. Flower extracts might have stronger effects on miR128/193a-5p/335 level changes than branch-body extracts. Hypericum perforatum extracts exerted weaker cytotoxic effects on 3D HeLa spheroids when compared with their effects on 2D monolayer HeLa cells. Taken together, results of our research may suggest the promising anticancer properties of the Hypericum perforatum extracts. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.",
journal = "Cytotechnology",
title = "Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models",
volume = "73",
number = "3",
pages = "373-389",
doi = "10.1007/s10616-021-00464-5"
}

Matić, I. Z., Ergün, S., Đorđić Crnogorac, M., Misir, S., Aliyazicioğlu, Y., Damjanović, A., Džudžević-Čančar, H., Stanojković, T. P., Konanç, K.,& Petrović, N.. (2021). Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models. in Cytotechnology, 73(3), 373-389.
https://doi.org/10.1007/s10616-021-00464-5

Matić IZ, Ergün S, Đorđić Crnogorac M, Misir S, Aliyazicioğlu Y, Damjanović A, Džudžević-Čančar H, Stanojković TP, Konanç K, Petrović N. Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models. in Cytotechnology. 2021;73(3):373-389.
doi:10.1007/s10616-021-00464-5 .

Matić, Ivana Z., Ergün, Sercan, Đorđić Crnogorac, Marija, Misir, Sema, Aliyazicioğlu, Yüksel, Damjanović, Ana, Džudžević-Čančar, Hurija, Stanojković, Tatjana P., Konanç, Kalbiye, Petrović, Nina, "Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models" in Cytotechnology, 73, no. 3 (2021):373-389,
https://doi.org/10.1007/s10616-021-00464-5 . .

TY  - JOUR
AU  - Ergun, Sercan
AU  - Güney, Serkan
AU  - Temiz, Ebru
AU  - Petrović, Nina
AU  - Gunes, Sezgin
PY  - 2019
UR  - http://www.eurekaselect.com/163857/article
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8099
AB  - Background: In recent years, targeted cancer treatment methods at various molecular levels have been developed for Non-Small Cell Lung Cancer (NSCLC), one of two major subtypes of lung cancer. miRNAbased clinical trials are currently the preferred targeted therapeutic strategy. Also, ceRNAs (competing endogenous RNA) would be the newest and the most effective approach to uncover novel interactions between mRNAs and miRNAs in NSCLC carcinogenesis. There are many factors influencing the efficiency of a miRNA to suppress or silence translation of the target mRNA. The most effective event is the presence of other RNAs showing ceRNA activity. These RNAs contain binding sites for specific miRNAs and enable miRNAs to bind these pseudo targets, instead of the original binding sites on the target mRNA. Therefore, the mRNA of the target gene is less affected by this miRNA, while the amount of miRNA remains the same in the media. Method: For this project, we determined that five clinically important different oncogenes (PDL1, FGFR1, DDX3X, SLC1A5, FXR1) are involved in the pathogenesis of NSCLC. For this purpose, we transfected model NSCLC cell line, A549, with miRNAs (miR-150-5p, miR-15a-5p, miR-503-5p) targeting these oncogenes to investigate whether these oncogenes will be suppressed at the mRNA level and also how the suppression efficiency of these miRNA on the oncogenes will be affected by possible ceRNA (CNKSR3, POU2F1, HIPK2) activities. Results: miR-15a-5p was determined to have the most suppressive effect on the five genes and three potential ceRNAs (p<0.05). Furthermore, CNKSR3 was the ceRNA most affected by all three miRNAs (p<0.05). Conclusion: CNKSR3 was affected more than the oncogenes known to act on NSCLC and this might make it a stronger and novel marker for use in possible treatment regimens designed using miR-15a-5p silencing effect on oncogenes in NSCLC pathogenesis. According to the literature, this is the first study associating NSCLC with miR-15a-5p and CNKSR3. © 2018 Bentham Science Publishers.
T2  - Anti-Cancer Agents in Medicinal Chemistry
T1  - Significance of miR-15a-5p and CNKSR3 as Novel Prognostic Biomarkers in Non-Small Cell Lung Cancer
VL  - 18
IS  - 12
SP  - 1695
EP  - 1701
DO  - 10.2174/1871520618666180718100656
ER  - 

@article{
author = "Ergun, Sercan and Güney, Serkan and Temiz, Ebru and Petrović, Nina and Gunes, Sezgin",
year = "2019",
abstract = "Background: In recent years, targeted cancer treatment methods at various molecular levels have been developed for Non-Small Cell Lung Cancer (NSCLC), one of two major subtypes of lung cancer. miRNAbased clinical trials are currently the preferred targeted therapeutic strategy. Also, ceRNAs (competing endogenous RNA) would be the newest and the most effective approach to uncover novel interactions between mRNAs and miRNAs in NSCLC carcinogenesis. There are many factors influencing the efficiency of a miRNA to suppress or silence translation of the target mRNA. The most effective event is the presence of other RNAs showing ceRNA activity. These RNAs contain binding sites for specific miRNAs and enable miRNAs to bind these pseudo targets, instead of the original binding sites on the target mRNA. Therefore, the mRNA of the target gene is less affected by this miRNA, while the amount of miRNA remains the same in the media. Method: For this project, we determined that five clinically important different oncogenes (PDL1, FGFR1, DDX3X, SLC1A5, FXR1) are involved in the pathogenesis of NSCLC. For this purpose, we transfected model NSCLC cell line, A549, with miRNAs (miR-150-5p, miR-15a-5p, miR-503-5p) targeting these oncogenes to investigate whether these oncogenes will be suppressed at the mRNA level and also how the suppression efficiency of these miRNA on the oncogenes will be affected by possible ceRNA (CNKSR3, POU2F1, HIPK2) activities. Results: miR-15a-5p was determined to have the most suppressive effect on the five genes and three potential ceRNAs (p<0.05). Furthermore, CNKSR3 was the ceRNA most affected by all three miRNAs (p<0.05). Conclusion: CNKSR3 was affected more than the oncogenes known to act on NSCLC and this might make it a stronger and novel marker for use in possible treatment regimens designed using miR-15a-5p silencing effect on oncogenes in NSCLC pathogenesis. According to the literature, this is the first study associating NSCLC with miR-15a-5p and CNKSR3. © 2018 Bentham Science Publishers.",
journal = "Anti-Cancer Agents in Medicinal Chemistry",
title = "Significance of miR-15a-5p and CNKSR3 as Novel Prognostic Biomarkers in Non-Small Cell Lung Cancer",
volume = "18",
number = "12",
pages = "1695-1701",
doi = "10.2174/1871520618666180718100656"
}

Ergun, S., Güney, S., Temiz, E., Petrović, N.,& Gunes, S.. (2019). Significance of miR-15a-5p and CNKSR3 as Novel Prognostic Biomarkers in Non-Small Cell Lung Cancer. in Anti-Cancer Agents in Medicinal Chemistry, 18(12), 1695-1701.
https://doi.org/10.2174/1871520618666180718100656

Ergun S, Güney S, Temiz E, Petrović N, Gunes S. Significance of miR-15a-5p and CNKSR3 as Novel Prognostic Biomarkers in Non-Small Cell Lung Cancer. in Anti-Cancer Agents in Medicinal Chemistry. 2019;18(12):1695-1701.
doi:10.2174/1871520618666180718100656 .

Ergun, Sercan, Güney, Serkan, Temiz, Ebru, Petrović, Nina, Gunes, Sezgin, "Significance of miR-15a-5p and CNKSR3 as Novel Prognostic Biomarkers in Non-Small Cell Lung Cancer" in Anti-Cancer Agents in Medicinal Chemistry, 18, no. 12 (2019):1695-1701,
https://doi.org/10.2174/1871520618666180718100656 . .

TY  - JOUR
AU  - Petrović, Nina
AU  - Ergun, Sercan
AU  - Isenović, Esma R.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1736
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, involved in the silencing of messenger RNA (mRNA) translation. The importance of miRNA signatures in disease screening, prognosis, and progression of different tumor types and subtypes is increasing. miRNA expression levels change depending on numerous factors. In this review, we are describing the circumstances under which miRNA levels can change, these are named levels of heterogeneity of miRNAs. miRNAs can have oncogenic, tumor suppressive, or both roles depending on tumor type and target mRNA whose translation they silence. The expression levels of a single miRNA may vary across different cancer types and subtypes, indicating that a miRNA signature may be tissue specific. miRNA levels of expression also vary during disease formation and propagation, indicating the presence of a time profile for their expression. The complexity of the miRNA-mRNA interference network mirrors different genetic and epigenetic changes that influence miRNA and mRNA availability to each other, and hence, their binding ability. The potential role of miRNAs as biomarkers is two-fold; first, for monitoring of the phases of cancer pathogenesis, and second, to characterize the particular type/subtype of cancer. It is important that a particular miRNA should be characterized by examining as many types and subtypes of cancers as are available, as well as being extracted from different types of samples, in order to obtain a complete picture of its behavior and importance in the disease pathology.
T2  - Molecular Diagnosis and Therapy
T1  - Levels of MicroRNA Heterogeneity in Cancer Biology
VL  - 21
IS  - 5
SP  - 511
EP  - 523
DO  - 10.1007/s40291-017-0285-9
ER  - 

@article{
author = "Petrović, Nina and Ergun, Sercan and Isenović, Esma R.",
year = "2017",
abstract = "MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, involved in the silencing of messenger RNA (mRNA) translation. The importance of miRNA signatures in disease screening, prognosis, and progression of different tumor types and subtypes is increasing. miRNA expression levels change depending on numerous factors. In this review, we are describing the circumstances under which miRNA levels can change, these are named levels of heterogeneity of miRNAs. miRNAs can have oncogenic, tumor suppressive, or both roles depending on tumor type and target mRNA whose translation they silence. The expression levels of a single miRNA may vary across different cancer types and subtypes, indicating that a miRNA signature may be tissue specific. miRNA levels of expression also vary during disease formation and propagation, indicating the presence of a time profile for their expression. The complexity of the miRNA-mRNA interference network mirrors different genetic and epigenetic changes that influence miRNA and mRNA availability to each other, and hence, their binding ability. The potential role of miRNAs as biomarkers is two-fold; first, for monitoring of the phases of cancer pathogenesis, and second, to characterize the particular type/subtype of cancer. It is important that a particular miRNA should be characterized by examining as many types and subtypes of cancers as are available, as well as being extracted from different types of samples, in order to obtain a complete picture of its behavior and importance in the disease pathology.",
journal = "Molecular Diagnosis and Therapy",
title = "Levels of MicroRNA Heterogeneity in Cancer Biology",
volume = "21",
number = "5",
pages = "511-523",
doi = "10.1007/s40291-017-0285-9"
}

Petrović, N., Ergun, S.,& Isenović, E. R.. (2017). Levels of MicroRNA Heterogeneity in Cancer Biology. in Molecular Diagnosis and Therapy, 21(5), 511-523.
https://doi.org/10.1007/s40291-017-0285-9

Petrović N, Ergun S, Isenović ER. Levels of MicroRNA Heterogeneity in Cancer Biology. in Molecular Diagnosis and Therapy. 2017;21(5):511-523.
doi:10.1007/s40291-017-0285-9 .

Petrović, Nina, Ergun, Sercan, Isenović, Esma R., "Levels of MicroRNA Heterogeneity in Cancer Biology" in Molecular Diagnosis and Therapy, 21, no. 5 (2017):511-523,
https://doi.org/10.1007/s40291-017-0285-9 . .