The Long Noncoding RNA LINC00963 Inhibits Corneal Fibrosis Scar Formation by Targeting miR-143-3p

Abstract

Corneal fibrosis is a complication of severe corneal injury, one of the major causes of vision loss. The formation of myofibroblasts has emerged as a key stimulative factor of corneal fibrosis. In the current study, we focused on the role of LINC00963 in regulating corneal fibrosis. Transforming growth factor β1 (TGF-β1) was used to induce human corneal stromal cells differentiating into corneal myofibroblasts, and the significant increase of α-smooth muscle actin (α-SMA) was verified by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescence, respectively. LINC00963 was identified to be one-half decreased compared with nonstimulated human corneal stromal cells, indicating that it might play a role in corneal fibrosis. Interestingly, overexpression of LINC00963 resulted in decreased formation of myofibroblasts indicating that it might exhibit an inhibiting effect. Moreover, bioinformatics tool was applied to predict the downstream target of LINC00963. We investigated that LINC00963 suppressed α-SMA induced by TGF-β1 in corneal fibroblasts, at least in part, by downregulating the expression of miR-143-3p. In addition, either LINC00963 promotion or miR-143-3p inhibition could significantly decrease myofibroblast contractility and collagen I and III secretion, which are the key to contribute to corneal fibrosis. Taken together, our study identified LINC00963 as a promising therapeutic target.

Targeting MetaLnc9/miR-143/FSCN1 axis inhibits oxidative stress and myofibroblast transdifferentiation in oral submucous fibrosis

“…3 A). One of the previous studies has shown that MetaLnc9 regulated the TGF-β1-induced myofibroblast transdifferentiation of corneal fibroblasts by sponging miR-143-3p, 12 which also mediates subconjunctival fibrosis. 17 Hence, we examined whether MetaLnc9 physically interacted with miR-143.…”

“…Of note, it has been revealed that MetaLnc9 inhibits the TGF-β1-elicited myofibroblast transdifferentiation of corneal fibroblasts as well as lowers the secretion of collagen I and III by downregulating miR-143-3p. 12 As such, it is intriguing to inspect whether MetaLnc9 is pro-fibrosis or anti-fibrosis during myofibroblast transdifferentiation of BMFs and associated molecular mechanisms.…”

MicroRNA of Epithelial to Mesenchymal Transition in Fuchs’ Endothelial Corneal Dystrophy

“…miRNAs were suggested as potential biomarkers of different diseases, including certain corneal diseases, and were also proposed as possible treatment targets [ 47 , 48 ].…”

“…EMT is one of the key embryological mechanisms, and involves epithelial cells losing their polarity and obtaining mesenchymal properties. EMT also participates in tissue repair; inflammation; fibrosis, including fibrosis of the cornea after trauma or infection; and tumor metastasis [ 48 , 49 ].…”

Corneal Epithelial Regeneration: Old and New Perspectives

“…For instance, miR-205 promotes the spread of epithelial cells to the site of corneal damage upregulating the AKT- and F-actin-mediated pathways [ 110 ] and inhibiting the KCNJ10 channel [ 111 ]. Moreover, miRNA-143-3p inhibition downregulates the expression of α-SMA, thereby reducing contractility of myofibroblasts and thus the tissue fibrotic response [ 112 ]. MiRNA-200a also inhibits fibrosis blocking corneal epithelial cell migration [ 113 ].…”