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  1. Article ; Online: The TGFBI gene and protein expression in topotecan resistant ovarian cancer cell lines.

    Wojtowicz, Karolina / Świerczewska, Monika / Nowicki, Michał / Januchowski, Radosław

    Advances in medical sciences

    2023  Volume 68, Issue 2, Page(s) 379–385

    Abstract: Purpose: The primary limiting factor in achieving cures for patients with cancer, particularly ovarian cancer, is drug resistance. The mechanisms of drug resistance of cancer cells during chemotherapy may include compounds of the extracellular matrix, ... ...

    Abstract Purpose: The primary limiting factor in achieving cures for patients with cancer, particularly ovarian cancer, is drug resistance. The mechanisms of drug resistance of cancer cells during chemotherapy may include compounds of the extracellular matrix, such as the transforming growth factor-beta-induced protein (TGFBI). In this study, we aimed to analyze the TGFBI gene and protein expression in different sensitive and drug-resistant ovarian cancer cell lines, as well as test if TGFBI can be involved in the response to topotecan (TOP) at the very early stages of treatment.
    Materials and methods: In this study, we conducted a detailed analysis of TGFBI expression in different ovarian cancer cell lines (A2780, A2780TR1, A2780TR2, W1, W1TR, SKOV-3, PEA1, PEA2 and PEO23). The level of TGFBI mRNA (QPCR), intracellular and extracellular protein (Western blot analysis) were assessed in this study.
    Results: We observed upregulation of TGFBI mRNA in drug-resistant cell lines and estrogen-receptor positive cell lines, which was supported by overexpression of both intracellular and extracellular TGFBI protein. We also showed the TGFBI expression after a short period of treatment of sensitive ovarian cancer cell lines with TOP.
    Conclusion: The expression of TGFBI in ovarian cancer cell lines suggests its role in the development of drug resistance.
    MeSH term(s) Female ; Humans ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; RNA, Messenger ; Topotecan/pharmacology ; Topotecan/therapeutic use ; Transforming Growth Factor beta
    Chemical Substances RNA, Messenger ; Topotecan (7M7YKX2N15) ; Transforming Growth Factor beta ; betaIG-H3 protein (148710-76-3)
    Language English
    Publishing date 2023-10-06
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2273668-2
    ISSN 1898-4002 ; 1896-1126
    ISSN (online) 1898-4002
    ISSN 1896-1126
    DOI 10.1016/j.advms.2023.09.013
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  2. Article ; Online: Drug resistance evaluation in novel 3D in vitro model.

    Nowacka, Marta / Sterzynska, Karolina / Andrzejewska, Malgorzata / Nowicki, Michal / Januchowski, Radoslaw

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2021  Volume 138, Page(s) 111536

    Abstract: Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high mortality is the development of drug resistance. It can be related to changes in the expression of many drug resistance genes as well as expression ... ...

    Abstract Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high mortality is the development of drug resistance. It can be related to changes in the expression of many drug resistance genes as well as expression of extracellular matrix proteins and cell density in the tumor. We developed a simple two-dimensional and three-dimensional model of drug sensitive A2780 and resistant to cisplatin and paclitaxel variants of ovarian cancer cell line. Using MTT assay, we compared drug resistance in two-dimensional and three-dimensional cell culture conditions. Real-time polymerase chain reaction analysis was used to compare the expression of drug resistance genes. The expression of proteins in spheroids was determined by immunohistochemistry. We observed a moderate increase in cisplatin resistance and a significant increase in paclitaxel resistance between two-dimensional and three-dimensional cell culture conditions. Our findings show that changes in the expression of drug resistance genes may play a crucial role in the drug resistance of cancer cells in traditional cell culture. On the other hand, the drug resistance in spheroids may result from different mechanisms such as cell density in the spheroid, extracellular matrix proteins expression and drug capacity to diffuse into the spheroid.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Cell Communication ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Paclitaxel/pharmacology
    Chemical Substances Antineoplastic Agents ; Paclitaxel (P88XT4IS4D) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2021-03-31
    Publishing country France
    Document type Comparative Study ; Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2021.111536
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  3. Article ; Online: The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Cisplatin- and Paclitaxel-Resistant Ovarian Cancer Cell Lines.

    Kazmierczak, Dominika / Jopek, Karol / Sterzynska, Karolina / Nowicki, Michal / Rucinski, Marcin / Januchowski, Radoslaw

    International journal of molecular sciences

    2022  Volume 23, Issue 1

    Abstract: Ovarian cancer is the most lethal gynecological malignancy. The high mortality results from late diagnosis and the development of drug resistance. Drug resistance results from changes in the expression of different drug-resistance genes that may be ... ...

    Abstract Ovarian cancer is the most lethal gynecological malignancy. The high mortality results from late diagnosis and the development of drug resistance. Drug resistance results from changes in the expression of different drug-resistance genes that may be regulated miRNA. The main aim of our study was to detect changes in miRNA expression levels in two cisplatin (CIS) and two paclitaxel (PAC)-resistant variants of the A2780 drug-sensitive ovarian cancer cell line-by miRNA microarray. The next goal was to identify miRNAs responsible for the regulation of drug-resistance genes. We observed changes in the expression of 46 miRNA that may be related to drug resistance. The overexpression of miR-125b-5p, miR-99a-5p, miR-296-3p, and miR-887-3p and downregulation of miR-218-5p, miR-221-3p, and miR-222-3p was observed in both CIS-resistant cell lines. In both PAC-resistant cell lines, we observed the upregulation of miR-221-3p, miR-222-3p, and miR-4485, and decreased expression of miR-551b-3p, miR-551b-5p, and miR-218-5p. Analysis of targets suggest that expression of important drug-resistant genes like protein Tyrosine Phosphatase Receptor Type K (
    MeSH term(s) Biomarkers, Tumor ; Cell Line, Tumor ; Cisplatin/pharmacology ; Computational Biology/methods ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; MicroRNAs/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Paclitaxel/pharmacology ; RNA Interference
    Chemical Substances Biomarkers, Tumor ; MicroRNAs ; Paclitaxel (P88XT4IS4D) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2022-01-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23010526
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  4. Article ; Online: The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Cisplatin- and Paclitaxel-Resistant Ovarian Cancer Cell Lines

    Dominika Kazmierczak / Karol Jopek / Karolina Sterzynska / Michal Nowicki / Marcin Rucinski / Radoslaw Januchowski

    International Journal of Molecular Sciences, Vol 23, Iss 526, p

    2022  Volume 526

    Abstract: Ovarian cancer is the most lethal gynecological malignancy. The high mortality results from late diagnosis and the development of drug resistance. Drug resistance results from changes in the expression of different drug-resistance genes that may be ... ...

    Abstract Ovarian cancer is the most lethal gynecological malignancy. The high mortality results from late diagnosis and the development of drug resistance. Drug resistance results from changes in the expression of different drug-resistance genes that may be regulated miRNA. The main aim of our study was to detect changes in miRNA expression levels in two cisplatin (CIS) and two paclitaxel (PAC)—resistant variants of the A2780 drug-sensitive ovarian cancer cell line—by miRNA microarray. The next goal was to identify miRNAs responsible for the regulation of drug-resistance genes. We observed changes in the expression of 46 miRNA that may be related to drug resistance. The overexpression of miR-125b-5p, miR-99a-5p, miR-296-3p, and miR-887-3p and downregulation of miR-218-5p, miR-221-3p, and miR-222-3p was observed in both CIS-resistant cell lines. In both PAC-resistant cell lines, we observed the upregulation of miR-221-3p, miR-222-3p, and miR-4485, and decreased expression of miR-551b-3p, miR-551b-5p, and miR-218-5p. Analysis of targets suggest that expression of important drug-resistant genes like protein Tyrosine Phosphatase Receptor Type K ( PTPRK ), receptor tyrosine kinase— EPHA7 , Semaphorin 3A ( SEMA3A ), or the ATP-binding cassette subfamily B member 1 gene ( ABCB1 ) can be regulated by miRNA.
    Keywords ovarian cancer ; first line chemotherapy ; microRNA ; drug-resistant genes ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
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  5. Article ; Online: The response and resistance to drugs in ovarian cancer cell lines in 2D monolayers and 3D spheroids.

    Świerczewska, Monika / Sterzyńska, Karolina / Ruciński, Marcin / Andrzejewska, Małgorzata / Nowicki, Michał / Januchowski, Radosław

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2023  Volume 165, Page(s) 115152

    Abstract: Ovarian cancer is the most common type of gynecologic cancer. One of the leading causes of high mortality is chemoresistance, developed primarily or during treatment. Different mechanisms of drug resistance appear at the cellular and cancer tissue ... ...

    Abstract Ovarian cancer is the most common type of gynecologic cancer. One of the leading causes of high mortality is chemoresistance, developed primarily or during treatment. Different mechanisms of drug resistance appear at the cellular and cancer tissue organization levels. We examined the differences in response to the cytotoxic drugs CIS, MTX, DOX, VIN, PAC, and TOP using 2D (two-dimensional) and 3D (three-dimensional) culture methods. We tested the drug-sensitive ovarian cancer cell line W1 and established resistant cell lines to appropriate cytotoxic drugs. The following qualitative and quantitative methods were used to assess: 1) morphology - inverted microscope and hematoxylin & eosin staining; 2) viability - MTT assay; 3) gene expression - a quantitative polymerase chain reaction; 4) identification of proteins - immunohistochemistry, and immunofluorescence. Our results indicate that the drug-sensitive and drug-resistant cells cultured in 3D conditions exhibit stronger resistance than the cells cultured in 2D conditions. A traditional 2D model shows that drug resistance of cancer cells is caused mainly by changes in the expression of genes encoding ATP-binding cassette transporter proteins, components of the extracellular matrix, "new" established genes related to drug resistance in ovarian cancer cell lines, and universal marker of cancer stem cells. Whereas in a 3D model, the drug resistance in spheroids can be related to other mechanisms such as the structure of the spheroid (dense or loose), the cell type (necrotic, quiescent, proliferating cells), drug concentrations or drug diffusion into the dense cellular/ECM structure.
    MeSH term(s) Drug Resistance, Neoplasm ; Ovarian Neoplasms/chemistry ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Cell Line, Tumor ; Humans ; Female ; Spheroids, Cellular ; Cell Culture Techniques, Three Dimensional ; Antineoplastic Agents/pharmacology
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2023-07-11
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2023.115152
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  6. Article ; Online: Semaphorin 3A (SEMA3A), protocadherin 9 (PCdh9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of different neoplasms, including ovarian cancer - review of literature.

    Izycka, Natalia / Sterzynska, Karolina / Januchowski, Radoslaw / Nowak-Markwitz, Ewa

    Ginekologia polska

    2019  Volume 90, Issue 4, Page(s) 223–227

    Abstract: Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Its high mortality rate results from lack of adequate and sensitive methods allowing for the detection of the early stages of the disease, as well as low efficiency of the ... ...

    Abstract Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Its high mortality rate results from lack of adequate and sensitive methods allowing for the detection of the early stages of the disease, as well as low efficiency of the treatment, caused by the cytotoxic drug resistance of cancer cells. Unfortunately, tumours are able to develop new pathways and protective mechanisms that allow them to survive toxic conditions of chemotherapy. Therefore, intensive search for new genes and proteins involved in resistance to cytotoxic drugs is still needed, especially from a clinical point of view. The article presents an overview of the available literature on the role of semaphorin 3A (SEMA3A), protocadherin 9 (PCDH9), and S100 calcium binding protein A3 (S100A3) in carcinogenesis and chemoresistance of various tumors including ovarian cancer. As it turns out, the role of described genes/proteins is not limited only to their native biological activity but they function also as an oncogenic or suppressor factors in the tumor development. Moreover, they can also play an important role in development of drug resistance, as it was shown in ovarian cancer cell lines.
    MeSH term(s) Antineoplastic Agents ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/metabolism ; Cadherins/analysis ; Cadherins/metabolism ; Drug Resistance, Neoplasm ; Female ; Humans ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/metabolism ; S100 Proteins/analysis ; S100 Proteins/metabolism ; Semaphorin-3A/analysis ; Semaphorin-3A/metabolism
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Cadherins ; PCDH9 protein, human ; S100 Proteins ; S100A3 protein, human ; SEMA3A protein, human ; Semaphorin-3A
    Language English
    Publishing date 2019-05-06
    Publishing country Poland
    Document type Journal Article
    ZDB-ID 130894-4
    ISSN 2543-6767 ; 0017-0011
    ISSN (online) 2543-6767
    ISSN 0017-0011
    DOI 10.5603/GP.2019.0040
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  7. Article ; Online: Effect of

    Nowacka, Marta / Ginter-Matuszewska, Barbara / Świerczewska, Monika / Sterzyńska, Karolina / Nowicki, Michał / Januchowski, Radosław

    International journal of molecular sciences

    2022  Volume 23, Issue 6

    Abstract: Ovarian cancer is the most common cause of gynecological cancer death. Cancer Stem Cells (CSCs) characterized by drug transporters and extracellular matrix (ECM) molecules expression are responsible for drug resistance development. The goal of our study ... ...

    Abstract Ovarian cancer is the most common cause of gynecological cancer death. Cancer Stem Cells (CSCs) characterized by drug transporters and extracellular matrix (ECM) molecules expression are responsible for drug resistance development. The goal of our study was to examine the role of aldehyde dehydrogenase 1A1 (ALDH1A1) expression in paclitaxel (PAC) and topotecan (TOP) resistant ovarian cancer cell lines. In both cell lines, we knocked out the
    MeSH term(s) ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; Aldehyde Dehydrogenase/genetics ; Aldehyde Dehydrogenase/metabolism ; Aldehyde Dehydrogenase 1 Family ; Carcinoma, Ovarian Epithelial/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Humans ; Neoplasm Proteins/metabolism ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Paclitaxel/pharmacology ; Retinal Dehydrogenase/genetics ; Retinal Dehydrogenase/metabolism ; Topotecan/pharmacology
    Chemical Substances ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Neoplasm Proteins ; Topotecan (7M7YKX2N15) ; Aldehyde Dehydrogenase 1 Family (EC 1.2.1) ; Aldehyde Dehydrogenase (EC 1.2.1.3) ; ALDH1A1 protein, human (EC 1.2.1.36) ; Retinal Dehydrogenase (EC 1.2.1.36) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2022-03-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23063036
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  8. Article ; Online: The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Doxorubicin and Topotecan Resistant Ovarian Cancer Cell Lines.

    Stasiak, Piotr / Kaźmierczak, Dominika / Jopek, Karol / Nowicki, Michał / Rucinski, Marcin / Januchowski, Radosław

    International journal of molecular sciences

    2022  Volume 23, Issue 10

    Abstract: Epithelial ovarian cancer has the highest mortality among all gynecological malignancies. The main reasons for high mortality are late diagnosis and development of resistance to chemotherapy. Resistance to chemotherapeutic drugs can result from altered ... ...

    Abstract Epithelial ovarian cancer has the highest mortality among all gynecological malignancies. The main reasons for high mortality are late diagnosis and development of resistance to chemotherapy. Resistance to chemotherapeutic drugs can result from altered expression of drug-resistance genes regulated by miRNA. The main goal of our study was to detect differences in miRNA expression levels in two doxorubicin (DOX)- and two topotecan (TOP)-resistant variants of the A2780 drug-sensitive ovarian cancer cell line by miRNA microarray. The next aim was to recognize miRNAs as factors responsible for the regulation of drug-resistance genes. We observed altered expression of 28 miRNA that may be related to drug resistance. The upregulation of miR-125b-5p and miR-935 and downregulation of miR-218-5p was observed in both DOX-resistant cell lines. In both TOP-resistant cell lines, we noted the overexpression of miR-99a-5p, miR-100-5p, miR-125b-5p, and miR-125b-2-3p and decreased expression of miR-551b-3p, miR-551b-5p, and miR-383-5p. Analysis of the targets suggested that expression of important drug-resistant genes such as the collagen type I alpha 2 chain (
    MeSH term(s) Carcinoma, Ovarian Epithelial ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Female ; Humans ; MicroRNAs/metabolism ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Topotecan/pharmacology
    Chemical Substances MIRN218 microRNA, human ; MIRN383 microRNA, human ; MicroRNAs ; Topotecan (7M7YKX2N15) ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2022-05-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23105846
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  9. Article ; Online: vPARP Adjusts MVP Expression in Drug-resistant Cell Lines in Conjunction with MDR Proteins.

    Wojtowicz, Karolina / Januchowski, Radoslaw / Nowicki, Michal / Zabel, Maciej

    Anticancer research

    2017  Volume 37, Issue 6, Page(s) 3015–3023

    Abstract: Background/aim: The definition of vault (ribonucleoprotein particles) function remains highly complex. Vaults may cooperate with multidrug resistance (MDR) proteins, supporting their role in drug resistance. This topic is the main theme of this ... ...

    Abstract Background/aim: The definition of vault (ribonucleoprotein particles) function remains highly complex. Vaults may cooperate with multidrug resistance (MDR) proteins, supporting their role in drug resistance. This topic is the main theme of this publication.
    Materials and methods: The cell viability was determined by an MTT assay. The protein expression was detected by western blot analysis. The proteins were knocked-down using siRNA.
    Results: No major vault protein (MVP) in the LoVo/Dx and W1PR cell lines after tunicamycin treatment was shown. In W1PR cells with knocked-down MVP, a statistically significant decrease in cell viability was noted. In LoVo/Dx, W1TR and A2780TR cells were vault poly-ADP-ribose polymerase (vPARP) was knockdown, a decrease in cell viability was shown. Also, MVP silencing induced an increase in glycoprotein P (Pgp) expression in LoVo/Dx cells.
    Conclusion: MVP is important for the drug resistance of cancer cells, but it probably requires the presence of vPARP for full activation. Some correlations between MDR proteins and vaults exist.
    MeSH term(s) ATP Binding Cassette Transporter, Sub-Family B/genetics ; ATP Binding Cassette Transporter, Sub-Family B/metabolism ; Antineoplastic Agents/pharmacology ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Drug Resistance, Multiple/physiology ; Drug Resistance, Neoplasm/physiology ; Gene Silencing ; Humans ; Poly(ADP-ribose) Polymerases/genetics ; Poly(ADP-ribose) Polymerases/metabolism ; Vault Ribonucleoprotein Particles/genetics ; Vault Ribonucleoprotein Particles/metabolism
    Chemical Substances ATP Binding Cassette Transporter, Sub-Family B ; Antineoplastic Agents ; Carrier Proteins ; TEP1 protein, human ; Vault Ribonucleoprotein Particles ; major vault protein ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; vault poly(ADP-ribose) polymerase (EC 2.4.2.30)
    Language English
    Publishing date 2017
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 604549-2
    ISSN 1791-7530 ; 0250-7005
    ISSN (online) 1791-7530
    ISSN 0250-7005
    DOI 10.21873/anticanres.11656
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  10. Article ; Online: The Profile of MicroRNA Expression and Potential Role in the Regulation of Drug-Resistant Genes in Doxorubicin and Topotecan Resistant Ovarian Cancer Cell Lines

    Piotr Stasiak / Dominika Kaźmierczak / Karol Jopek / Michał Nowicki / Marcin Rucinski / Radosław Januchowski

    International Journal of Molecular Sciences, Vol 23, Iss 5846, p

    2022  Volume 5846

    Abstract: Epithelial ovarian cancer has the highest mortality among all gynecological malignancies. The main reasons for high mortality are late diagnosis and development of resistance to chemotherapy. Resistance to chemotherapeutic drugs can result from altered ... ...

    Abstract Epithelial ovarian cancer has the highest mortality among all gynecological malignancies. The main reasons for high mortality are late diagnosis and development of resistance to chemotherapy. Resistance to chemotherapeutic drugs can result from altered expression of drug-resistance genes regulated by miRNA. The main goal of our study was to detect differences in miRNA expression levels in two doxorubicin (DOX)- and two topotecan (TOP)-resistant variants of the A2780 drug-sensitive ovarian cancer cell line by miRNA microarray. The next aim was to recognize miRNAs as factors responsible for the regulation of drug-resistance genes. We observed altered expression of 28 miRNA that may be related to drug resistance. The upregulation of miR-125b-5p and miR-935 and downregulation of miR-218-5p was observed in both DOX-resistant cell lines. In both TOP-resistant cell lines, we noted the overexpression of miR-99a-5p, miR-100-5p, miR-125b-5p, and miR-125b-2-3p and decreased expression of miR-551b-3p, miR-551b-5p, and miR-383-5p. Analysis of the targets suggested that expression of important drug-resistant genes such as the collagen type I alpha 2 chain ( COL1A2 ), protein Tyrosine Phosphatase Receptor Type K ( PTPRK ), receptor tyrosine kinase— EPHA7 , Roundabout Guidance Receptor 2 ( ROBO2 ), myristoylated alanine-rich C-kinase substrate ( MARCK ), and the ATP-binding cassette subfamily G member 2 ( ABCG2 ) can be regulated by miRNA.
    Keywords ovarian cancer ; second line chemotherapy ; microRNA ; drug-resistant genes ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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