lncRNA H19 contributes to oxidative damage repair in the early age‐related cataract by regulating miR‐29a/TDG axis

Abstract

Age‐related cataract (ARC) is caused by the exposure of the lens to UVB which promotes oxidative damage and cell death. This study aimed to explore the role of lncRNA H19 in oxidative damage repair in early ARC. lncRNAs sequencing technique was used to identify different lncRNAs in the lens of early ARC patients. Human lens epithelial cells (HLECs) were exposed to ultraviolet irradiation; and 8‐OHdG ELISA, Cell counting kit 8 (CCK8), EDU, flow cytometry and TUNEL assays were used to detect DNA damage, cell viability, proliferation and apoptosis. Luciferase assay was used to examine the interaction among H19, miR‐29a and thymine DNA glycosylase (TDG) 3'UTR. We found that lncRNA H19 and TDG were highly expressed while miR‐29a was down‐regulated in the three types of early ARC and HLECs exposed to ultraviolet irradiation, compared to respective controls. lncRNA H19 knockdown aggravated oxidative damage, reduced cell viability and proliferation, and promoted apoptosis in HLECs, while lncRNA H19 overexpression led to opposite effects in HLECs. Mechanistically, miR‐29a bound TDG 3'UTR to repress TDG expression. lncRNA H19 up‐regulated the expression of TDG by repressing miR‐29a because it acted as ceRNA through sponging miR‐29a. In conclusion, the interaction among lncRNA H19, miR‐29a and TDG is involved in early ARC. lncRNA H19 could be a useful marker of early ARC and oxidative damage repair pathway of lncRNA H19/miR‐29a/TDG may be a promising target for the treatment of ARC.

RETRACTED ARTICLE: Role of short-wavelength blue light in the formation of cataracts and the expression of caspase-1, caspase-11, Gasdermin D in rat lens epithelial cells: insights into a novel pathogenic mechanism of cataracts

“…A cell viability assay of LECs was performed via flow cytometry in 6-well plates [27]. When pyroptosis occurs in cells, membrane permeability increases.…”

Long non‑coding RNA NONHSAT143692.2 is involved in oxidative DNA damage repair in the lens by regulating the miR‑4728‑5p/OGG1 axis

“…LncRNAs and miRNAs play an important role in the apoptosis and proliferation of LEcs. They may be involved in the occurrence and development of ARc via different mechanisms; however, their association with OGG1 has not yet been reported (16)(17)(18)(19), at least to the best of our knowledge. We hypothesized that after oxidative stress, lncRNA and microRNA may increase the apoptosis of LEcs by inhibiting the function of OGG1, leading to lens opacity.…”

“…lncRNAs have important regulatory functions and can participate in the proliferation, apoptosis and migration of cells (13)(14)(15). Recently, a variety of lncRNAs playing key roles in ARc have been identified (16)(17)(18)(19). However, the regulation of OGG1 by lncRNAs has rarely been reported, at least to the best of our knowledge.…”

The Emerging Roles of Non-Coding RNAs in Cataract

“…LncRNA MIAT acts as a competing endogenous RNA (ceRNA) to sponge miR-150-5p and accelerates the proliferation and migration of HLECs [34]. LncH19 was up-regulated in ARC and act as ceRNA via H19/miR-29a/TDG pathway, which may be a promising target for the treatment [36]. Another study discovered that H19/miR-675 axis may affected CRYAA expression involved in the pathogenesis of nuclear ARC [33].…”

“…Emerging studies reveal that the dysregulation of lncRNAs are impact the development and progression of cataract [31] [32] [33] [34] [35]. Compared with transparent lenses, KCNQ1OT1, TUG1, and H19 has identified to have signifi-cantly increased expression in age-related cataract [36] [37] [38]. The significant differential expression of lncRNAs in age-related cataract human lenses indicates that lncRNAs might play a crucial role in cataract formation ( Table 2).…”