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.

Liu L ，Yang X ，Zhang J ，Jiang W ，Hou T ，Zong Y ，Bai H ，Yang K ，Yang X ... -  《-》

lncRNA SNHG11 promotes lung cancer cell proliferation and migration via activation of Wnt/β-catenin signaling pathway.

Lung cancer ranks topmost among the most frequently diagnosed cancers. Despite increasing research, there are still unresolved mysteries in the molecular mechanism of lung cancer. Long noncoding RNA small nucleolar RNA host gene 11 (SNHG11) was found to be upregulated in lung cancer and facilitated lung cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression while suppressed cell apoptosis. Moreover, the high expression of SNHG11 was correlated with poor prognosis of lung cancer patients, TNM stage, and tumor size. Further assays demonstrated that SNHG11 functioned in lung cancer cells via Wnt/β-catenin signaling pathway. Subsequently, Wnt/β-catenin pathway was found to be activated through SNHG11/miR-4436a/CTNNB1 ceRNA axis. As inhibiting miR-4436 could only partly rescue the suppression of cell function induced by silencing SNHG11, it was suspected that β-catenin might enter cell nucleus through other pathways. Mechanism investigation proved that SNHG11 would directly bind with β-catenin to activate classic Wnt pathway. Subsequently, in vivo tumorigenesis was also demonstrated to be enhanced by SNHG11. Hence, SNHG11 was found to promote lung cancer progression by activating Wnt/β-catenin pathway in two different patterns, implying that SNHG11 might contribute to lung cancer treatment by acting as a therapeutic target.

Liu S ，Yang N ，Wang L ，Wei B ，Chen J ，Gao Y ... -  《-》

lncRNA SNHG11 Promotes Gastric Cancer Progression by Activating the Wnt/β-Catenin Pathway and Oncogenic Autophagy.

Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3β ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/β-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent on ATG12 rather than the Wnt/β-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC.

Wu Q ，Ma J ，Wei J ，Meng W ，Wang Y ，Shi M ... -  《-》

GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.

Sugali CK ，Rayana NP ，Dai J ，Harvey DH ，Dhamodaran K ，Mao W ... -  《-》

Long noncoding RNA OIP5-AS1 targets Wnt-7b to affect glioma progression via modulation of miR-410.

The present study was undertaken to investigate the underlying mechanisms of long noncoding RNA OIP5-AS1 via regulating miR-410 to modulate Wnt-7b in the progression of glioma. To address this problem, we measured the expression of OIP5-AS1 and miR-410 in glioma tissues by qRT-PCR. Glioma U87 cells were transfected with OIP5-AS1 siRNA or miR-410 inhibitors. The targeting relationships among miR-410, OIP5-AS1 and Wnt-7b were verified by luciferase reporter assays. Western blotting was employed to determine the expression of Wnt-7b/β-catenin pathway-related proteins, while MTT, flow cytometry, Transwell assays and wound-healing assays were used to measure the biological characteristics of glioma cells. The results showed that OIP5-AS1 expression was higher and miR-410 was lower in glioma tissues. Luciferase reporter assays confirmed a targeting relationship between OIP5-AS1 and miR-410, as well as between miR-410 and Wnt-7b. Silencing OIP5-AS1 reduced cell proliferation, invasion and migration of glioma U87 cells and led to depressed expression levels of miR-410, Wnt-7b, p-β-catenin, GSK-3β-pS9, c-Myc and cyclin D1. Furthermore, down-regulation of OIP5-AS1 induced G0/G1 phase cell cycle arrest and apoptosis of glioma cells. Inhibitors of miR-410 abolished the biological effects of OIP5-AS1 siRNA in glioma cells. In vivo, OIP5-AS1 knockdown also inhibited tumor growth. Taken together, this research suggested that silencing OIP5-AS1 may specifically block the Wnt-7b/β-catenin pathway via targeted up-regulating miR-410, thereby inhibiting growth, invasion and migration while promoting apoptosis in glioma cells.

Sun WL ，Kang T ，Wang YY ，Sun JP ，Li C ，Liu HJ ，Yang Y ，Jiao BH ... -  《-》