Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients
Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable fa...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/464 |
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| author | Natalia Yunusova Ekaterina Dzhugashvili Alena Yalovaya Larisa Kolomiets Aleksei Shefer Alina Grigor’eva Alexey Tupikin Irina Kondakova Svetlana Tamkovich |
| author_facet | Natalia Yunusova Ekaterina Dzhugashvili Alena Yalovaya Larisa Kolomiets Aleksei Shefer Alina Grigor’eva Alexey Tupikin Irina Kondakova Svetlana Tamkovich |
| author_sort | Natalia Yunusova |
| collection | DOAJ |
| description | Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, <i>p</i> < 0.05) and plasma exosomal miR-24 (R = 0.74, <i>p</i> < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors. |
| first_indexed | 2024-03-11T09:58:37Z |
| format | Article |
| id | doaj.art-234733584e8a4f5286a8b3b6d205e042 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:58:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-234733584e8a4f5286a8b3b6d205e0422023-11-16T15:33:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124146410.3390/ijms24010464Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer PatientsNatalia Yunusova0Ekaterina Dzhugashvili1Alena Yalovaya2Larisa Kolomiets3Aleksei Shefer4Alina Grigor’eva5Alexey Tupikin6Irina Kondakova7Svetlana Tamkovich8Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaV. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaV. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaV. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, RussiaOvarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, <i>p</i> < 0.05) and plasma exosomal miR-24 (R = 0.74, <i>p</i> < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.https://www.mdpi.com/1422-0067/24/1/464exosomestumor-specific microRNAsmiR-24-3pmiR-101CD151Tspan8 |
| spellingShingle | Natalia Yunusova Ekaterina Dzhugashvili Alena Yalovaya Larisa Kolomiets Aleksei Shefer Alina Grigor’eva Alexey Tupikin Irina Kondakova Svetlana Tamkovich Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients International Journal of Molecular Sciences exosomes tumor-specific microRNAs miR-24-3p miR-101 CD151 Tspan8 |
| title | Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients |
| title_full | Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients |
| title_fullStr | Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients |
| title_full_unstemmed | Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients |
| title_short | Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients |
| title_sort | comparative analysis of tumor associated micrornas and tetraspanines from exosomes of plasma and ascitic fluids of ovarian cancer patients |
| topic | exosomes tumor-specific microRNAs miR-24-3p miR-101 CD151 Tspan8 |
| url | https://www.mdpi.com/1422-0067/24/1/464 |
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