Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors
Sirtuins (SIRTs) are NAD<sup>+</sup>-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/2047 |
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| author | Nina Schmid Kim-Gwendolyn Dietrich Ignasi Forne Alexander Burges Magdalena Szymanska Rina Meidan Doris Mayr Artur Mayerhofer |
| author_facet | Nina Schmid Kim-Gwendolyn Dietrich Ignasi Forne Alexander Burges Magdalena Szymanska Rina Meidan Doris Mayr Artur Mayerhofer |
| author_sort | Nina Schmid |
| collection | DOAJ |
| description | Sirtuins (SIRTs) are NAD<sup>+</sup>-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1–7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs, these SIRTs may represent novel drug targets. |
| first_indexed | 2024-03-09T00:44:46Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:44:46Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-892d619744e14676ba22ca1d848877712023-12-11T17:36:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224204710.3390/ijms22042047Sirtuin 1 and Sirtuin 3 in Granulosa Cell TumorsNina Schmid0Kim-Gwendolyn Dietrich1Ignasi Forne2Alexander Burges3Magdalena Szymanska4Rina Meidan5Doris Mayr6Artur Mayerhofer7Cell Biology—Anatomy III, Biomedical Center (BMC), LMU München, Großhaderner Straße 9, 82152 Martinsried, GermanyCell Biology—Anatomy III, Biomedical Center (BMC), LMU München, Großhaderner Straße 9, 82152 Martinsried, GermanyProtein Analysis Unit, Biomedical Center (BMC), LMU München, Großhaderner Straße 9, 82152 Martinsried, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 81377 Munich, GermanyInstitute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, PolandDepartment of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 761001, IsraelInstitute of Pathology, University Hospital, LMU Munich, Thalkirchner Str. 36, 80377 Munich, GermanyCell Biology—Anatomy III, Biomedical Center (BMC), LMU München, Großhaderner Straße 9, 82152 Martinsried, GermanySirtuins (SIRTs) are NAD<sup>+</sup>-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1–7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs, these SIRTs may represent novel drug targets.https://www.mdpi.com/1422-0067/22/4/2047granulosa cell tumorKGNsirtuin 1sirtuin 3siRNA silencingEX 527 |
| spellingShingle | Nina Schmid Kim-Gwendolyn Dietrich Ignasi Forne Alexander Burges Magdalena Szymanska Rina Meidan Doris Mayr Artur Mayerhofer Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors International Journal of Molecular Sciences granulosa cell tumor KGN sirtuin 1 sirtuin 3 siRNA silencing EX 527 |
| title | Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors |
| title_full | Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors |
| title_fullStr | Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors |
| title_full_unstemmed | Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors |
| title_short | Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors |
| title_sort | sirtuin 1 and sirtuin 3 in granulosa cell tumors |
| topic | granulosa cell tumor KGN sirtuin 1 sirtuin 3 siRNA silencing EX 527 |
| url | https://www.mdpi.com/1422-0067/22/4/2047 |
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