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

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 (GTM₃ ) 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 GTM₃ 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 β-catenin phosphorylation at Ser33/37/Thr41 while decreasing β-catenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/β-catenin signaling through Rho/ROCK via β-catenin phosphorylation at Ser675 or GSK-3β-mediated phosphorylation at Ser33/37/Thr41, affecting cell proliferation, migration, Apoptosis, and Autophagy. Through its effects on Wnt/β-catenin signaling, SNHG11 is implicated in glaucoma pathogenesis and is a potential therapeutic target.

SNHG11; Wnt/beta-catenin signaling pathway; glaucoma; lncRNA; rho-associated kinase; trabecular meshwork.