microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2
Cells undergo apoptosis under dense culture condition to maintain homeostasis. Impaired apoptosis may contribute to the excessive accumulation of pathogenetic cells in such diseases as cancer and organ fibrosis. Elucidating the molecular mechanisms regulating cell density-dependent apoptosis may pro...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933525000196 |
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| author | Yuki Yabuuchi Yosuke Matsuno Kai Yazaki Wei Zhen Ting Kengo Nishino Sosuke Matsumura Kenya Kuramoto Kazufumi Yoshida Masashi Matsuyama Takumi Kiwamoto Yuko Morishima Nobuyuki Hizawa |
| author_facet | Yuki Yabuuchi Yosuke Matsuno Kai Yazaki Wei Zhen Ting Kengo Nishino Sosuke Matsumura Kenya Kuramoto Kazufumi Yoshida Masashi Matsuyama Takumi Kiwamoto Yuko Morishima Nobuyuki Hizawa |
| author_sort | Yuki Yabuuchi |
| collection | DOAJ |
| description | Cells undergo apoptosis under dense culture condition to maintain homeostasis. Impaired apoptosis may contribute to the excessive accumulation of pathogenetic cells in such diseases as cancer and organ fibrosis. Elucidating the molecular mechanisms regulating cell density-dependent apoptosis may provide novel therapeutic strategy against these diseases. We have reported Notch signaling, activated by γ-secretase under dense culture condition, regulates cell density-dependent apoptosis through the induction of IL-6. Presenilin 2 (PSEN2) is a subunit of γ-secretase and has been shown to modulate apoptosis. The role for PSEN2 in cell density-dependent apoptosis and Notch signaling activation, however, remains unclear. Here, we show a crucial role for PSEN2 in the regulation of cell density-dependent apoptosis in NIH 3T3 cells. PSEN2 protein primarily existed as C-terminal fragment (CTF). PSEN2 CTF expression was upregulated as cell density increased. PSEN2 regulated the development of apoptosis, which is accompanied by increased Bcl-2 expression, decreased Bax expression, and activated PI3K/Akt pathway. PSEN2 is predicted to be targeted by microRNA-183–5p (miR-183–5p) by several algorithms. We verified miR-183–5p directly regulates PSEN2 expression and induces apoptosis. In conclusion, our results demonstrate a crucial role of PSEN2 and its regulation by miR-183–5p in the regulation of cell density-dependent apoptosis. |
| format | Article |
| id | doaj-art-340b3fe21d3942cf92eb7a7c4bbf4b61 |
| institution | Kabale University |
| issn | 0171-9335 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj-art-340b3fe21d3942cf92eb7a7c4bbf4b612025-08-20T03:45:27ZengElsevierEuropean Journal of Cell Biology0171-93352025-06-01104215149410.1016/j.ejcb.2025.151494microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2Yuki Yabuuchi0Yosuke Matsuno1Kai Yazaki2Wei Zhen Ting3Kengo Nishino4Sosuke Matsumura5Kenya Kuramoto6Kazufumi Yoshida7Masashi Matsuyama8Takumi Kiwamoto9Yuko Morishima10Nobuyuki Hizawa11Department of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, Japan; Correspondence to: Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.Department of Pulmonary Medicine, Nikko Memorial Hospital, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanDepartment of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, JapanCells undergo apoptosis under dense culture condition to maintain homeostasis. Impaired apoptosis may contribute to the excessive accumulation of pathogenetic cells in such diseases as cancer and organ fibrosis. Elucidating the molecular mechanisms regulating cell density-dependent apoptosis may provide novel therapeutic strategy against these diseases. We have reported Notch signaling, activated by γ-secretase under dense culture condition, regulates cell density-dependent apoptosis through the induction of IL-6. Presenilin 2 (PSEN2) is a subunit of γ-secretase and has been shown to modulate apoptosis. The role for PSEN2 in cell density-dependent apoptosis and Notch signaling activation, however, remains unclear. Here, we show a crucial role for PSEN2 in the regulation of cell density-dependent apoptosis in NIH 3T3 cells. PSEN2 protein primarily existed as C-terminal fragment (CTF). PSEN2 CTF expression was upregulated as cell density increased. PSEN2 regulated the development of apoptosis, which is accompanied by increased Bcl-2 expression, decreased Bax expression, and activated PI3K/Akt pathway. PSEN2 is predicted to be targeted by microRNA-183–5p (miR-183–5p) by several algorithms. We verified miR-183–5p directly regulates PSEN2 expression and induces apoptosis. In conclusion, our results demonstrate a crucial role of PSEN2 and its regulation by miR-183–5p in the regulation of cell density-dependent apoptosis.http://www.sciencedirect.com/science/article/pii/S0171933525000196AktB cell lymphoma-2Notch signaling pathwaymicroRNA 183–5pPhosphatidylinositol-3 kinasePresenilin 2 |
| spellingShingle | Yuki Yabuuchi Yosuke Matsuno Kai Yazaki Wei Zhen Ting Kengo Nishino Sosuke Matsumura Kenya Kuramoto Kazufumi Yoshida Masashi Matsuyama Takumi Kiwamoto Yuko Morishima Nobuyuki Hizawa microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2 European Journal of Cell Biology Akt B cell lymphoma-2 Notch signaling pathway microRNA 183–5p Phosphatidylinositol-3 kinase Presenilin 2 |
| title | microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2 |
| title_full | microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2 |
| title_fullStr | microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2 |
| title_full_unstemmed | microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2 |
| title_short | microRNA-183–5p induces cell density-dependent apoptosis through the regulation of Presenilin 2 |
| title_sort | microrna 183 5p induces cell density dependent apoptosis through the regulation of presenilin 2 |
| topic | Akt B cell lymphoma-2 Notch signaling pathway microRNA 183–5p Phosphatidylinositol-3 kinase Presenilin 2 |
| url | http://www.sciencedirect.com/science/article/pii/S0171933525000196 |
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