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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Dove Medical Press
2021
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oai:doaj.org-article:dac299d5a76f4f04bbcca41b236757e22021-12-02T16:06:29ZMALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose1178-1998https://doaj.org/article/dac299d5a76f4f04bbcca41b236757e22021-06-01T00:00:00Zhttps://www.dovepress.com/malat1-regulated-mtor-mediated-tau-hyperphosphorylation-by-acting-as-a-peer-reviewed-fulltext-article-CIAhttps://doaj.org/toc/1178-1998Chong 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-144Lu CZhao YCao YLiu LWu SLi DLiu SXiao SWei YLi XDove Medical Pressarticlediabetes mellitustaumalat1mtormir-144GeriatricsRC952-954.6ENClinical Interventions in Aging, Vol Volume 16, Pp 1185-1191 (2021) |
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diabetes mellitus tau malat1 mtor mir-144 Geriatrics RC952-954.6 |
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diabetes mellitus tau malat1 mtor mir-144 Geriatrics RC952-954.6 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 |
| 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 |
| format |
article |
| 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 |
| title |
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_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_sort |
malat1 regulated mtor-mediated tau hyperphosphorylation by acting as a cerna of mir144 in hippocampus cells exposed to high glucose |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/dac299d5a76f4f04bbcca41b236757e2 |
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