N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract
N6-methyladenosine (m6A) is the most prevalent eukaryotic messenger RNA modification. Diabetic cataract (DC) is caused by high glucose (HG) in diabetes mellitus. However, the regulatory mechanism of m6A in the DC pathogenesis is poorly understood. In present research, we performed the m6A-RNA immuno...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-06-01
|
Series: | Molecular Therapy: Nucleic Acids |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120300743 |
_version_ | 1828376703110479872 |
---|---|
author | Jun Yang Jingshu Liu Shaozhen Zhao Fang Tian |
author_facet | Jun Yang Jingshu Liu Shaozhen Zhao Fang Tian |
author_sort | Jun Yang |
collection | DOAJ |
description | N6-methyladenosine (m6A) is the most prevalent eukaryotic messenger RNA modification. Diabetic cataract (DC) is caused by high glucose (HG) in diabetes mellitus. However, the regulatory mechanism of m6A in the DC pathogenesis is poorly understood. In present research, we performed the m6A-RNA immunoprecipitation sequencing (MeRIP-Seq) analysis and detected the m6A modification profile in the HG- or normal glucose (NG)-induced human lens epithelial cells (HLECs). Results revealed that methyltransferase-like 3 (METTL3) was upregulated in the DC tissue specimens and HG-induced HLECs. Besides, total m6A modification level was higher in the HG-induced HLECs. Functionally, METTL3 knockdown promoted the proliferation and repressed the apoptosis of HLECs induced by HG. MeRIP-Seq analysis revealed that ICAM-1 might act as the target of METTL3. Mechanistically, METTL3 targets the 3′ UTR of ICAM-1 to stabilize mRNA stability. In conclusion, this research identified the regulation of METTL3 in the HG-induced HLECs, providing a potential insight of the m6A modification for DC. |
first_indexed | 2024-04-14T08:02:53Z |
format | Article |
id | doaj.art-f2ac90cbf04c4347a7e35375b1e92e49 |
institution | Directory Open Access Journal |
issn | 2162-2531 |
language | English |
last_indexed | 2024-04-14T08:02:53Z |
publishDate | 2020-06-01 |
publisher | Elsevier |
record_format | Article |
series | Molecular Therapy: Nucleic Acids |
spelling | doaj.art-f2ac90cbf04c4347a7e35375b1e92e492022-12-22T02:04:50ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-06-0120111116N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic CataractJun Yang0Jingshu Liu1Shaozhen Zhao2Fang Tian3Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, ChinaTianjin University of Traditional Chinese Medicine, Tianjin, ChinaEye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China; Corresponding author: Shaozhen Zhao, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China; Corresponding author: Fang Tian, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.N6-methyladenosine (m6A) is the most prevalent eukaryotic messenger RNA modification. Diabetic cataract (DC) is caused by high glucose (HG) in diabetes mellitus. However, the regulatory mechanism of m6A in the DC pathogenesis is poorly understood. In present research, we performed the m6A-RNA immunoprecipitation sequencing (MeRIP-Seq) analysis and detected the m6A modification profile in the HG- or normal glucose (NG)-induced human lens epithelial cells (HLECs). Results revealed that methyltransferase-like 3 (METTL3) was upregulated in the DC tissue specimens and HG-induced HLECs. Besides, total m6A modification level was higher in the HG-induced HLECs. Functionally, METTL3 knockdown promoted the proliferation and repressed the apoptosis of HLECs induced by HG. MeRIP-Seq analysis revealed that ICAM-1 might act as the target of METTL3. Mechanistically, METTL3 targets the 3′ UTR of ICAM-1 to stabilize mRNA stability. In conclusion, this research identified the regulation of METTL3 in the HG-induced HLECs, providing a potential insight of the m6A modification for DC.http://www.sciencedirect.com/science/article/pii/S2162253120300743N6-methyladenosinehuman lens epithelial cellsdiabetic cataractMETTL3ICAM-1 |
spellingShingle | Jun Yang Jingshu Liu Shaozhen Zhao Fang Tian N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract Molecular Therapy: Nucleic Acids N6-methyladenosine human lens epithelial cells diabetic cataract METTL3 ICAM-1 |
title | N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract |
title_full | N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract |
title_fullStr | N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract |
title_full_unstemmed | N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract |
title_short | N6-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract |
title_sort | n6 methyladenosine mettl3 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract |
topic | N6-methyladenosine human lens epithelial cells diabetic cataract METTL3 ICAM-1 |
url | http://www.sciencedirect.com/science/article/pii/S2162253120300743 |
work_keys_str_mv | AT junyang n6methyladenosinemettl3modulatestheproliferationandapoptosisoflensepithelialcellsindiabeticcataract AT jingshuliu n6methyladenosinemettl3modulatestheproliferationandapoptosisoflensepithelialcellsindiabeticcataract AT shaozhenzhao n6methyladenosinemettl3modulatestheproliferationandapoptosisoflensepithelialcellsindiabeticcataract AT fangtian n6methyladenosinemettl3modulatestheproliferationandapoptosisoflensepithelialcellsindiabeticcataract |