Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

Abstract

Background/Aims: Age-related cataract (ARC) remains the leading cause of visual impairment among the elderly population. Long non-coding RNAs (lncRNAs) have emerged as potential regulators in many ocular diseases. However, the role of lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. Methods: LncRNA sequencing was performed to identify differentially expressed lncRNAs between the capsules of transparent and nuclear ARC lenses. Expression validation was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were used to determine the role of H19 or miR-675 in the viability, apoptosis, proliferation and migration of primary cultured human lens epithelial cells (HLECs). Bioinformatics and luciferase reporter assays were used to identify the binding target of miR-675. Results: Sixty-three lncRNAs are differentially expressed between the capsules of transparent and nuclear ARC lenses. One top abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown accelerates apoptosis development and reduces the proliferation and migration of HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting the binding site within the 3’UTR. Moreover, miR-675 increases the proliferation and migration while decreasing the apoptosis of HLECs upon oxidative stress. Conclusion: H19 regulates HLECs function through miR-675-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of nuclear ARC.

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

“…lncRNA is a class of non‐coding RNA molecules that transcribe more than 200 nucleotides and could not encode a protein because of the lack of an effective open reading frame (ORF) . Recently, several lncRNAs have been found to play a key role in ARC . In this study, we aimed to identify lncRNAs differentially expressed in ARC and elucidate their role in the pathogenesis of ARC.…”

LncRNA PLCD3-OT1 Functions as a CeRNA to Prevent Age-Related Cataract by Sponging miR-224-5p and Regulating PLCD3 Expression

“…LncRNAs, 15% of which are located in the cytoplasm, 18 are usually expressed in the stage-specific manner of disease, tissue, or development, indicating specific functions for lncRNAs in development and diseases and indicating that these molecules are attractive therapeutic targets. [19][20][21] An increasing number of studies have shown that lncRNAs are involved in the pathogenesis of several ocular diseases, including corneal neovascularization, 22 cataract, 23,24 glaucoma, 25 diabetic retinopathy, 22,26 proliferative vitreoretinopathy, 27,28 and ocular tumors. 29,30 Although the mechanism of ARC is not completely understand, age, sex, smoking, sunlight exposure, genetic predisposition, heavy drinking, and cardiovascular factors may contribute to ARC progression.…”

The Emerging Roles of Non-Coding RNAs in Cataract

“…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].…”

“…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]. CRYAA encodes the predominant structural protein participate in refractive properties and the maintenance of lens clarity.…”