Long non‐coding RNA SNHG11 regulates the Wnt/β‐catenin signaling pathway through rho/ROCK in trabecular meshwork cells

Abstract

Trabecular meshwork (TM) cell dysfunction is the leading cause of elevated intraocular pressure (IOP) and glaucoma. The long non-coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) is associated with cell proliferation and apoptosis, but its biological functions and role in glaucoma pathogenesis remain unclear. In the present study, we investigated the role of SNHG11 in TM cells using immortalized human TM and glaucomatous human TM (GTM 3 ) cells and an acute ocular hypertension mouse model. SNHG11 expression was depleted using siRNA targeting SNHG11. Transwell assays, quantitative real-time PCR analysis (qRT-PCR), western blotting, and CCK-8 assay were used to evaluate cell migration, apoptosis, autophagy, and proliferation. Wnt/β-catenin pathway activity was inferred from qRT-PCR, western blotting, immunofluorescence, and luciferase reporter and TOPFlash reporter assays. The expression of Rho kinases (ROCKs) was detected using qRT-PCR and western blotting. SNHG11 was downregulated in GTM 3 cells and mice with acute ocular hypertension. In TM cells, SNHG11 knockdown inhibited cell proliferation and migration, activated autophagy, and apoptosis, repressing the Wnt/β-catenin signaling pathway, and activated Rho/ROCK. Wnt/β-catenin signaling pathway activity increased in TM cells treated with ROCK inhibitor. SNHG11 regulated Wnt/β-catenin signaling through Rho/ROCK by increasing GSK-3β expression and βcatenin phosphorylation at Ser33/37/Thr41 while decreasing βcatenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/β-catenin signaling through Rho/ROCK via βcatenin phosphorylation at Ser675 or GSK-3β-mediated

Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review)

“…On the other hand, overexpression of XIAP and survivin can protect TM cells and ONH astrocytes from apoptosis induced by oxidative stress ( 208 ). Besides, a number of studies have identified that Rho/ROCK is involved in the pathogenesis of glaucoma ( 74 , 209 ). In patients with glaucoma, Rho/ROCK activation alters the cytoskeleton and increases TM cell adhesion, reducing aqueous humour outflow and increasing IOP ( 74 ).…”

“…In patients with glaucoma, Rho/ROCK activation alters the cytoskeleton and increases TM cell adhesion, reducing aqueous humour outflow and increasing IOP ( 74 ). Additionally, Liu et al ( 209 ) reported that the long non-coding RNA small nucleolar RNA host gene 11 regulates Wnt/β-catenin signalling through Rho/ROCK via β-catenin phosphorylation at Ser675 or through GSK-3β-mediated phosphorylation at Ser33/37/Thr41, affecting TM cell proliferation, migration, apoptosis and autophagy. Therefore, the absence of activation of prosurvival genes in patients with glaucoma is a potential explanation for the increased vulnerability of the optic nerve to elevated IOP ( 210 ).…”