TSC complex decrease the expression of mTOR by regulated miR-199b-3p
Abstract The TSC complex formed by TSC1 and TSC2 is the most important upstream negative regulator of mTORC1. Genetic variations in either TSC1 or TSC2 cause tuberous sclerosis complex (TSC) disease which is a rare autosomal dominant disorder resulting in impairment of multiple organ systems. In thi...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-85706-8 |
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| author | Na Zhao Qiuhong Xiong Ping Li Guangxin Chen Han Xiao Changxin Wu |
| author_facet | Na Zhao Qiuhong Xiong Ping Li Guangxin Chen Han Xiao Changxin Wu |
| author_sort | Na Zhao |
| collection | DOAJ |
| description | Abstract The TSC complex formed by TSC1 and TSC2 is the most important upstream negative regulator of mTORC1. Genetic variations in either TSC1 or TSC2 cause tuberous sclerosis complex (TSC) disease which is a rare autosomal dominant disorder resulting in impairment of multiple organ systems. In this study, besides a reported variation, c.2509_2512del (p.Asn837Valfs*11, p.N837fs) in TSC1, we found a de novo TSC2 variation c.1113delG (p.Gln371Hisfs*18, p.Q371fs), which these two mutation influence the formation of TSC complex. We found that the decrease of TSC complex with the appearance of the decreased miR-199b-3p expression. At the same time, the reduction of miR-199b-3p increased the expression of mTOR and the activation of mTORC1 and mTORC2, the additional miR-199b-3p caused the decrease the expression of mTOR and the activation of mTORC1 and mTORC2. In brief, our results may illustrate a novel mechanism of TSC caused by variations in either TSC1 or TSC2, and a new mTOR expression regulator, miR-199b-3p. |
| format | Article |
| id | doaj-art-589d6bd6ecfd45bfb06b2fa293855ad4 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-589d6bd6ecfd45bfb06b2fa293855ad42025-01-19T12:18:06ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-85706-8TSC complex decrease the expression of mTOR by regulated miR-199b-3pNa Zhao0Qiuhong Xiong1Ping Li2Guangxin Chen3Han Xiao4Changxin Wu5Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi UniversityKey Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institutes of Biomedical Sciences, Shanxi UniversityAbstract The TSC complex formed by TSC1 and TSC2 is the most important upstream negative regulator of mTORC1. Genetic variations in either TSC1 or TSC2 cause tuberous sclerosis complex (TSC) disease which is a rare autosomal dominant disorder resulting in impairment of multiple organ systems. In this study, besides a reported variation, c.2509_2512del (p.Asn837Valfs*11, p.N837fs) in TSC1, we found a de novo TSC2 variation c.1113delG (p.Gln371Hisfs*18, p.Q371fs), which these two mutation influence the formation of TSC complex. We found that the decrease of TSC complex with the appearance of the decreased miR-199b-3p expression. At the same time, the reduction of miR-199b-3p increased the expression of mTOR and the activation of mTORC1 and mTORC2, the additional miR-199b-3p caused the decrease the expression of mTOR and the activation of mTORC1 and mTORC2. In brief, our results may illustrate a novel mechanism of TSC caused by variations in either TSC1 or TSC2, and a new mTOR expression regulator, miR-199b-3p.https://doi.org/10.1038/s41598-025-85706-8TSC1TSC2MTORMiR-199b-3pTSC |
| spellingShingle | Na Zhao Qiuhong Xiong Ping Li Guangxin Chen Han Xiao Changxin Wu TSC complex decrease the expression of mTOR by regulated miR-199b-3p Scientific Reports TSC1 TSC2 MTOR MiR-199b-3p TSC |
| title | TSC complex decrease the expression of mTOR by regulated miR-199b-3p |
| title_full | TSC complex decrease the expression of mTOR by regulated miR-199b-3p |
| title_fullStr | TSC complex decrease the expression of mTOR by regulated miR-199b-3p |
| title_full_unstemmed | TSC complex decrease the expression of mTOR by regulated miR-199b-3p |
| title_short | TSC complex decrease the expression of mTOR by regulated miR-199b-3p |
| title_sort | tsc complex decrease the expression of mtor by regulated mir 199b 3p |
| topic | TSC1 TSC2 MTOR MiR-199b-3p TSC |
| url | https://doi.org/10.1038/s41598-025-85706-8 |
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