LncRNA MALAT1 Regulates miR-144-3p to Facilitate Epithelial-Mesenchymal Transition of Lens Epithelial Cells via the ROSNRF2Notch1Snail Pathway
Joint Authors
Ye, Wei
Ma, Jiyuan
Wang, Fang
Wu, Tong
He, Mengmei
Li, Ji
Pei, Rui
Zhang, Luning
Wang, Yafen
Zhou, Jian
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-23, 23 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-11-16
Country of Publication
Egypt
No. of Pages
23
Main Subjects
Abstract EN
Diabetic cataract is a common complication of diabetes.
The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key event in the development of diabetic cataracts.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be highly expressed in different tissues of diabetic patients.
This study is aimed at investigating the function and mechanism of MALAT1 in the regulation of EMT in human LECs under high glucose conditions.
MALAT1, α-smooth muscle actin (α-SMA), fibronectin (FN), and nuclear factor erythroid-derived 2-like 2 (NRF2) were highly expressed in the LECs of diabetic cataract patients and in the human LECs under high glucose conditions; meanwhile, the decreased expressions of E-cadherin and zonula occludens 1 (ZO-1) were detected.
Knockdown of MALAT1 could significantly reduce ROS, prevent EMT, arrest S phase cell cycle, and suppress the expression of total NRF2 and its nucleus translocation in LECs.
Furthermore, after NRF2 was knocked down, total NRF2, α-SMA, and FN in cells, and NRF2, Notch intracellular domain (NICD), and Snail were decreased in the nucleus.
Using bioinformatics methods, we predicted that MALAT1 and NRF2 shared the same microRNA-144-3p (miR-144-3p) combining site.
Luciferase reporter coupled with qRT-PCR assays revealed that miR-144-3p was a target of MALAT1, which was confirmed to downregulate miR-144-3p in the LECs.
In addition, after transfection of miR-144-3p mimics or inhibitor, western blot assay demonstrated that miR-144-3p negatively regulated the expression of total NRF2, α-SMA, and FN in cells, and NRF2, NICD, and Snail in the nucleus without affecting Kelch-like ECH-associated protein 1 (KEAP1).
Finally, we confirmed that transfection of shMALAT1 inhibited NRF2 expression, and its mediated EMT could be rescued by miR-144-3p inhibitor; transfection of pcDNA3.1-MALAT1 promoted NRF2 expression, and its mediated EMT could be reversed by miR-144-3p inhibitor.
In summary, we demonstrate that MALAT1 regulates miR-144-3p to facilitate EMT of LECs via the ROS/NRF2/Notch1/Snail pathway.
American Psychological Association (APA)
Ye, Wei& Ma, Jiyuan& Wang, Fang& Wu, Tong& He, Mengmei& Li, Ji…[et al.]. 2020. LncRNA MALAT1 Regulates miR-144-3p to Facilitate Epithelial-Mesenchymal Transition of Lens Epithelial Cells via the ROSNRF2Notch1Snail Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-23.
https://search.emarefa.net/detail/BIM-1205535
Modern Language Association (MLA)
Ye, Wei…[et al.]. LncRNA MALAT1 Regulates miR-144-3p to Facilitate Epithelial-Mesenchymal Transition of Lens Epithelial Cells via the ROSNRF2Notch1Snail Pathway. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-23.
https://search.emarefa.net/detail/BIM-1205535
American Medical Association (AMA)
Ye, Wei& Ma, Jiyuan& Wang, Fang& Wu, Tong& He, Mengmei& Li, Ji…[et al.]. LncRNA MALAT1 Regulates miR-144-3p to Facilitate Epithelial-Mesenchymal Transition of Lens Epithelial Cells via the ROSNRF2Notch1Snail Pathway. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-23.
https://search.emarefa.net/detail/BIM-1205535
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205535