MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose
Chong Lu,1,* Yikui Zhao,2,* Yan Cao,3,* Li Liu,1 Shanshan Wu,1 Dongbin Li,1 Shuang Liu,1 Shuyuan Xiao,1 Yafen Wei,1 Xinyu Li3 1Department of Neurology, Heilongjiang Provincial Hospital, Harbin, People’s Republic of China; 2HIT Center for Life Sciences, School of Life Science and Technology...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-06-01
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| Series: | Clinical Interventions in Aging |
| Subjects: | |
| Online Access: | https://www.dovepress.com/malat1-regulated-mtor-mediated-tau-hyperphosphorylation-by-acting-as-a-peer-reviewed-fulltext-article-CIA |
| _version_ | 1818845061565120512 |
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| author | Lu C Zhao Y Cao Y Liu L Wu S Li D Liu S Xiao S Wei Y Li X |
| author_facet | Lu C Zhao Y Cao Y Liu L Wu S Li D Liu S Xiao S Wei Y Li X |
| author_sort | Lu C |
| collection | DOAJ |
| description | Chong Lu,1,* Yikui Zhao,2,* Yan Cao,3,* Li Liu,1 Shanshan Wu,1 Dongbin Li,1 Shuang Liu,1 Shuyuan Xiao,1 Yafen Wei,1 Xinyu Li3 1Department of Neurology, Heilongjiang Provincial Hospital, Harbin, People’s Republic of China; 2HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People’s Republic of China; 3Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyu Li; Yafen Wei Tel +86-13796658016; Tel +86-13796658016Email 13796658016@163.com; weiyafen2008@sina.comAim: High glucose (HG)-induced activation of mTOR promotes tau phosphorylation and leads to diabetes-associated dementia. This study aimed to explore the role of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in HG-induced neuronal cell injury.Methods: Hippocampus cells were isolated from C57BL/6J mice. After 6 days of culture, the cells were incubated with 5.5 mM glucose in normal medium or 75 mM glucose for 4 days. Cells were transfected with miR-144 mimic, miR-144 inhibitor, siRNA for MALAT1 or corresponding controls. Gene expression was detected by PCR and Western blot analysis.Results: HG increased the levels of MALAT1 and p-tau in hippocampal cells. Knockdown of MALAT1 partially reversed the effects of HG on mTOR activity and p-tau protein levels. MALAT1 functioned as competing endogenous RNA (ceRNA) for miR-144, and pre-treatment with MALAT1 siRNA decreased mTOR activity and p-tau protein level in HG-treated hippocampal cells, which was significantly attenuated by miR-144 mimics. Moreover, miR-144 negatively regulated the expression of mTOR and knockdown of MALAT1 suppressed mTOR, while overexpression of mTOR abrogated protective effects of MALAT1 knockdown in HG-treated hippocampal cells.Conclusion: MALAT1 knockdown prevented HG-induced mTOR activation and inhibited tau phosphorylation. MALAT1 may be a therapy target for diabetes associated dementia.Keywords: diabetes mellitus, tau, MALAT1, mTOR, miR-144 |
| first_indexed | 2024-12-19T05:23:40Z |
| format | Article |
| id | doaj.art-dac299d5a76f4f04bbcca41b236757e2 |
| institution | Directory Open Access Journal |
| issn | 1178-1998 |
| language | English |
| last_indexed | 2024-12-19T05:23:40Z |
| publishDate | 2021-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Interventions in Aging |
| spelling | doaj.art-dac299d5a76f4f04bbcca41b236757e22022-12-21T20:34:27ZengDove Medical PressClinical Interventions in Aging1178-19982021-06-01Volume 161185119166133MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High GlucoseLu CZhao YCao YLiu LWu SLi DLiu SXiao SWei YLi XChong Lu,1,* Yikui Zhao,2,* Yan Cao,3,* Li Liu,1 Shanshan Wu,1 Dongbin Li,1 Shuang Liu,1 Shuyuan Xiao,1 Yafen Wei,1 Xinyu Li3 1Department of Neurology, Heilongjiang Provincial Hospital, Harbin, People’s Republic of China; 2HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People’s Republic of China; 3Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyu Li; Yafen Wei Tel +86-13796658016; Tel +86-13796658016Email 13796658016@163.com; weiyafen2008@sina.comAim: High glucose (HG)-induced activation of mTOR promotes tau phosphorylation and leads to diabetes-associated dementia. This study aimed to explore the role of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in HG-induced neuronal cell injury.Methods: Hippocampus cells were isolated from C57BL/6J mice. After 6 days of culture, the cells were incubated with 5.5 mM glucose in normal medium or 75 mM glucose for 4 days. Cells were transfected with miR-144 mimic, miR-144 inhibitor, siRNA for MALAT1 or corresponding controls. Gene expression was detected by PCR and Western blot analysis.Results: HG increased the levels of MALAT1 and p-tau in hippocampal cells. Knockdown of MALAT1 partially reversed the effects of HG on mTOR activity and p-tau protein levels. MALAT1 functioned as competing endogenous RNA (ceRNA) for miR-144, and pre-treatment with MALAT1 siRNA decreased mTOR activity and p-tau protein level in HG-treated hippocampal cells, which was significantly attenuated by miR-144 mimics. Moreover, miR-144 negatively regulated the expression of mTOR and knockdown of MALAT1 suppressed mTOR, while overexpression of mTOR abrogated protective effects of MALAT1 knockdown in HG-treated hippocampal cells.Conclusion: MALAT1 knockdown prevented HG-induced mTOR activation and inhibited tau phosphorylation. MALAT1 may be a therapy target for diabetes associated dementia.Keywords: diabetes mellitus, tau, MALAT1, mTOR, miR-144https://www.dovepress.com/malat1-regulated-mtor-mediated-tau-hyperphosphorylation-by-acting-as-a-peer-reviewed-fulltext-article-CIAdiabetes mellitustaumalat1mtormir-144 |
| spellingShingle | Lu C Zhao Y Cao Y Liu L Wu S Li D Liu S Xiao S Wei Y Li X MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose Clinical Interventions in Aging diabetes mellitus tau malat1 mtor mir-144 |
| title | MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose |
| title_full | MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose |
| title_fullStr | MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose |
| title_full_unstemmed | MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose |
| title_short | MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose |
| title_sort | malat1 regulated mtor mediated tau hyperphosphorylation by acting as a cerna of mir144 in hippocampus cells exposed to high glucose |
| topic | diabetes mellitus tau malat1 mtor mir-144 |
| url | https://www.dovepress.com/malat1-regulated-mtor-mediated-tau-hyperphosphorylation-by-acting-as-a-peer-reviewed-fulltext-article-CIA |
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