Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis

Background. The ocular inflammatory microenvironment has been reported to be closely associated with the occurrence and progression of highly myopic cataract (HMC). Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could alter the biological properties of mammalian c...

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Main Authors: Yaru Hu, Xue Han, Yue Chen, Jinbiao Cai, Juan Li, Yuchen Fan, Jianfeng Wang, Shanglun Xie
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Ophthalmology
Online Access:http://dx.doi.org/10.1155/2023/9942880
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author Yaru Hu
Xue Han
Yue Chen
Jinbiao Cai
Juan Li
Yuchen Fan
Jianfeng Wang
Shanglun Xie
author_facet Yaru Hu
Xue Han
Yue Chen
Jinbiao Cai
Juan Li
Yuchen Fan
Jianfeng Wang
Shanglun Xie
author_sort Yaru Hu
collection DOAJ
description Background. The ocular inflammatory microenvironment has been reported to be closely associated with the occurrence and progression of highly myopic cataract (HMC). Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could alter the biological properties of mammalian cells by modulating the expression of inflammatory mediators; therefore, it may contribute to the development of HMC. Objective. To investigate the function of MALAT1 in the inflammatory response, proliferation, migration, and epithelial-mesenchymal transition (EMT) of inflammatory and injured human lens epithelial cells (HLECs) and to reveal the underlying molecular signals. Methods. Patients with HMC and age-related cataract (ARC) with an axial length of more than 26 mm were selected, and the anterior capsular tissue was obtained during cataract surgery. TNF-α (20 ng/mL) was chosen to induce inflammatory damage in HLECs to simulate the inflammatory microenvironment in HMC eyes. Specific siRNAs, inhibitors, and mimics were used to suppress or enhance the functions of MALAT1 and miR-26a-5p. RT-qPCR and Western blot analysis were performed to measure gene and protein expression, respectively. Results. The expression of MALAT1 and the inflammatory mediators IL-6, MMP-2, and MMP-9 were significantly higher in HMC anterior capsule tissues than in ARC. TNF-α treatment increased the expression of MALAT1, while it also promoted the proliferation, migration, and EMT of HLECs. MALAT1 interference decreased the expression of IL-6 and MMP-2 and inhibited the aforementioned processes. Furthermore, MALAT1 negatively regulated the expression of miR-26a-5p and then promoted TET1 expression. TET1 was identified as a direct target of miR-26a-5p, and the promoting effect of MALAT1 on TET1 expression could be reversed by miR-26a-5p mimics. Conclusion. The inflammatory environment and MALAT1 expression could be reciprocally induced in HLECs. MALAT1 may act as a ceRNA via the “sponge” miR-26a-5p and target TET1 to regulate the inflammatory response, proliferation, migration, and EMT processes in HLECs.
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spelling doaj-art-b5b792dcdbbf4900a3fb8fc41396b6c32025-08-20T03:20:55ZengWileyJournal of Ophthalmology2090-00582023-01-01202310.1155/2023/9942880Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling AxisYaru Hu0Xue Han1Yue Chen2Jinbiao Cai3Juan Li4Yuchen Fan5Jianfeng Wang6Shanglun Xie7Department of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologySchool of Life SciencesBackground. The ocular inflammatory microenvironment has been reported to be closely associated with the occurrence and progression of highly myopic cataract (HMC). Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could alter the biological properties of mammalian cells by modulating the expression of inflammatory mediators; therefore, it may contribute to the development of HMC. Objective. To investigate the function of MALAT1 in the inflammatory response, proliferation, migration, and epithelial-mesenchymal transition (EMT) of inflammatory and injured human lens epithelial cells (HLECs) and to reveal the underlying molecular signals. Methods. Patients with HMC and age-related cataract (ARC) with an axial length of more than 26 mm were selected, and the anterior capsular tissue was obtained during cataract surgery. TNF-α (20 ng/mL) was chosen to induce inflammatory damage in HLECs to simulate the inflammatory microenvironment in HMC eyes. Specific siRNAs, inhibitors, and mimics were used to suppress or enhance the functions of MALAT1 and miR-26a-5p. RT-qPCR and Western blot analysis were performed to measure gene and protein expression, respectively. Results. The expression of MALAT1 and the inflammatory mediators IL-6, MMP-2, and MMP-9 were significantly higher in HMC anterior capsule tissues than in ARC. TNF-α treatment increased the expression of MALAT1, while it also promoted the proliferation, migration, and EMT of HLECs. MALAT1 interference decreased the expression of IL-6 and MMP-2 and inhibited the aforementioned processes. Furthermore, MALAT1 negatively regulated the expression of miR-26a-5p and then promoted TET1 expression. TET1 was identified as a direct target of miR-26a-5p, and the promoting effect of MALAT1 on TET1 expression could be reversed by miR-26a-5p mimics. Conclusion. The inflammatory environment and MALAT1 expression could be reciprocally induced in HLECs. MALAT1 may act as a ceRNA via the “sponge” miR-26a-5p and target TET1 to regulate the inflammatory response, proliferation, migration, and EMT processes in HLECs.http://dx.doi.org/10.1155/2023/9942880
spellingShingle Yaru Hu
Xue Han
Yue Chen
Jinbiao Cai
Juan Li
Yuchen Fan
Jianfeng Wang
Shanglun Xie
Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis
Journal of Ophthalmology
title Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis
title_full Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis
title_fullStr Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis
title_full_unstemmed Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis
title_short Regulation of the Inflammatory Response, Proliferation, Migration, and Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells by the lncRNA-MALAT1/miR-26a-5p/TET1 Signaling Axis
title_sort regulation of the inflammatory response proliferation migration and epithelial mesenchymal transition of human lens epithelial cells by the lncrna malat1 mir 26a 5p tet1 signaling axis
url http://dx.doi.org/10.1155/2023/9942880
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