Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer

Purpose Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. Methods PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. Results In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. Conclusion Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.

Oseltamivir (Tamiflu)-induced bilateral acute angle closure glaucoma and transient myopia.

A 27-year-old woman developed bilateral acute angle closure glaucoma (AACG) and transient myopia after taking oseltamivir for four days. On the fourth day, she received systemic and topical intraocular pressure (IOP)-lowering agents, and IOP decreased in both eyes. However, her visual acuity was unchanged. A myopic shift of -5.25 D OD and -5.0 D OS was estimated to have occurred in the acute phase. A-scan ultrasonography and Pentacam showed markedly shallow anterior chambers and increased lens thickness. Ultrasound biomicroscopy revealed an annular ciliochoroidal effusion with forward displacement of the lens-iris diaphragm. Ciliochoroidal effusion and transient myopia were resolved after discontinuation of oseltamivir.

A subconjunctival foreign body confused with uveal prolapse.

There are cases in which the presence of a foreign body (FB) is difficult to diagnose based on history taking or clinical examination. We report a case of subconjunctival FB confused with uveal prolapse. A 68‑year‑old man, who had the history of pterygium excision in his right eye, complained of irritation and congestion in that same eye. He also had the history of growing vegetables in a plastic greenhouse. It seemed to be a suspected uveal mass bulging through a focal scleral thinning site. On the basis of slit‑lamp magnification, the lesion was presumed to be a hard and black keratinized mass embedded under the conjunctiva. Histopathologically, the removed mass was revealed to be a seed of the dicotyledones. Patients who show signs of prolapsed uvea or scleral thinning, possibility of a subconjunctival FB should be considered as differential diagnosis. In addition, a removed unknown FB should be examined histopathologically.

Intraocular pressure and influencing systemic health parameters in a Korean population.

Aim: To evaluate the relationship between intraocular pressure (IOP) and systemic health parameters such as age, gender, body mass index (BMI), total cholesterol, high density lipoprotein (HDL), and triglyceride (TG) in a Korean population. Materials and Methods: A total of 30,893 healthy subjects underwent automated multiphasic tests, including non‑contact tonometry, automated perimetry, fundus photography, and blood samplings for total cholesterol, HDL, and TG. Seven age groups were divided by decades ranging from 20 to 29 years to 80 + years. The association between IOP and BMI, plasma lipid profiles was examined using cross‑sectional analysis. Results: The mean age of subjects was 47.7 years. The mean IOP of subjects was 15.4 ± 3.2 mmHg for both eyes. The mean IOP of men was significantly higher than women (P = 0.000). By multiple linear regression analysis, IOP was positively associated with gender (male), BMI, total cholesterol, and TG and negatively associated with age (P = 0.000). BMI, total cholesterol, and TG had significantly positive correlations with IOP after adjusting for age, gender, and other variables which can influence the IOP (P = 0.000). Conclusions: In a Korean population, the mean IOP, total cholesterol, TG, and BMI values of men were higher than women. IOP was found to increase with total cholesterol, TG, BMI, and to decrease with only age regardless of sex.