MicroRNA-93 is overexpressed and induces apoptosis in glaucoma trabecular meshwork cells

Abstract

Glaucoma is an optic neuropathy and a major cause of blindness globally. Trabecular meshwork cells are important in maintaining aqueous humor flow, the dysfunction of which tends to induce glaucoma. As important regulators of gene expression, microRNAs may be crucial in regulating trabecular meshwork cells. The present study aimed to reveal the effect of microRNA‑93 (miR‑93) on glaucoma trabecular meshwork (GTM) cell apoptosis. The expression levels of miR‑93 were compared between human trabecular meshwork (HTM) cells and GTM cells. The expression of miR‑93 was inhibited and increased by transfecting the cells with a lentivirus containing its specific inhibitor sponge and expression vector to investigate changes in GTM cell viability and apoptosis. Alterations in the protein expression of nuclear factor erythroid 2‑like 2 (NFE2L2) were also examined to elucidate the possible mechanism underlying the effects of miR‑93. The results showed a marked promotion in the expression of miR‑93 in the GTM cells, compared with the HTM cells (P<0.01). GTM cell viability was increased and its apoptosis was inhibited by transfection with the miR‑93 sponge (P<0.01 and P<0.001, respectively), whereas the overexpression of miR‑93 abrogated these effects (P<0.05 and P<0.0001, respectively). The expression of NFE2L2, a possible target of miR‑93, was promoted by transfection with the miR‑93 sponge (P<0.01) and was inhibited in the cells overexpressing miR‑93 (P<0.01). Therefore, miR‑93 was capable of inhibiting viability and inducing apoptosis of the GTM cells, which was achieved via the suppression of NFE2L2. These results elucidated the pro‑apoptotic effects of miR‑93 in GTM cells and its possible functional mechanism, providing potential therapeutic targets for the treatment of glaucoma.

Expression of mRNAs, miRNAs, and lncRNAs in Human Trabecular Meshwork Cells Upon Mechanical Stretch

“…88 We also identified miR-93, which has been found to increase expression and induce apoptosis in glaucomatous TM cells. 89 Our integrative miRNA-mRNA expression analysis identified several miRNA-mRNA interactions in the TM cells, highlighting several miRNA master regulators, such as miR-125a-5p, miR-30a-3p, and miR-1275. Additional master miRNA regulators may be identified if we expand our analysis to include predicted targets with moderate confidence, although this would also potentially increase the number of false-positive findings.…”

Genome-wide Expression Profiling and Pathway Analysis in Cyclic Stretched Human Trabecular Meshwork Cells

“…miR-15a has been reported to be down-regulated in stress-induced senescent human TM cells (70). miR-93 was found to have increased expression in glaucomatous TM cells and induced apoptosis in these TM cells (71). Since our integrative analysis was restricted to only those experimentally validated miRNA targets, additional master miRNA regulators may be identified if we expanded our analysis to include predicted targets with high or moderate confidence, though this would potentially increase the number of false positive findings.…”

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

“…In 2017, Cheng et al found that compared with normal human trabecular meshwork cells, Nrf2 expression was down-regulated in glaucomatous trabecular meshwork cells, e921514-2 and in both cell types, the overexpression of Nrf2 promoted cell viability and reduced cell apoptosis [44]. Also, in 2016, Wang et al showed that microRNA-93 (miRNA-93) inhibited the cell viability and induced apoptosis of the glaucomatous trabecular meshwork cells via the suppression of Nrf2 [45]. These findings support the role of Nrf2 in protecting trabecular meshwork cells from oxidative stress.…”