Cisplatin has been widely used as a conventional treatment for patients with non-small cell lung cancer (NSCLC). However, primary and acquired cisplatin resistances are frequently developed during the treatment of patients with NSCLC, leading to an increased mortality rate. Accumulating evidence demonstrated that aberrantly expressed microRNAs (miRs) are involved in the development of chemoresistance. In the present study, sensitivity of NSCLC cells to cisplatin was identified to increase following overexpression of miR-608. Conversely, sensitivity to cisplatin was reduced following miR-608 knockdown. Reverse transcription-quantitative PCR and western blotting analyses identified that TEA domain transcription factor 2 (TEAD2), a key regulator of cell stemness, was negatively regulated by miR-608 in NSCLC cells. By repressing TEAD2, miR-608 decreased the expression level of several target genes of the Hippo-yes-associated protein signaling pathway. Furthermore, TEAD2 mRNA was confirmed to be targeted by miR-608 in NSCLC cells via a dual-luciferase reporter assay. Importantly, the increased cisplatin sensitivity induced by miR-608 overexpression was reversed by transfection of TEAD2 in NSCLC cells. The present data suggested that miR-608 may represent a novel candidate biomarker for the evaluation of cisplatin sensitivity in patients with NSCLC.
PURPOSE. N-methyl-N-nitrosourea (MNU) is an alkylating toxicant with potent mutagenic ability. This study was designed to induce apoptosis in lens epithelial cells (LECs) and corneal endothelial cells (CECs) via MNU administration. We sought to build ocular disease models of cataract and corneal endothelial decompensation. METHODS. MNU was delivered into the intraperitoneal cavities of neonatal rats and the anterior chambers of adult rabbits. The MNU-treated animals were then subjected to a series of functional and morphological analyses at various time points. RESULTS. MNU treatment induced pervasive apoptosis of LECs and CECs. These effects were dose and time dependent. Mature cataracts were found in neonatal rats 3 weeks after MNU treatment. Histological analysis revealed that MNU toxicity induced swelling, vacuolation, and liquefaction in lens fibers of MNU-treated rats. Pentacam examination showed that the average density of rat lens increased significantly after MNU administration. Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) analysis showed pervasive apoptotic staining in the lenses of MNU-treated rats. In rabbit eyes, intracameral treatment with MNU induced corneal edema and significantly increased central corneal thickness, which peaked at P14. Morphological and immunohistochemical analysis showed that CECs were effectively ablated in the MNU-treated rabbits. The expression of 8-OHdG increased significantly in the cornea of MNU-treated rabbits, compared with vehicle-treated controls. CONCLUSIONS. MNU is sufficient to induce ocular cell apoptosis in animal models. These models of MNU-induced cataract and corneal endothelial decompensation represent valuable tools for efforts to develop relevant therapies.
Ocular albinism type 1 (OA1) is a genetic disorder characterized by reduced eye pigmentation and nystagmus, which is often accompanied by decreased visual acuity, strabismus and other symptoms, whereas skin and hair color remain normal. The present study aimed to assess the clinical features and perform genotype analysis of a family with OA1, and to determine the disease-causing mutation. A total of 18 family members (nine affected patients and nine normal subjects) from Hainan, China, were recruited to the present study in December 2017. A detailed clinical ophthalmic examination was performed for all participants, including a visual acuity test, anterior segment slit lamp examination, eye fundus examination and optical coherence tomography. Mutations in the G protein-coupled receptor 143 (GPR143) gene were determined by DNA sequencing assays and polymerase chain reaction assays for deletions; all exon coding sequences, exons at the 5′- and 3′-ends, and non-coding region sequences of intron splicing were assessed. Within the family, nine male patients exhibited disease occurrence at the age of 0–6 months. All patients presented with different degrees of iris depigmentation, horizontal jerk nystagmus, foveal hypoplasia and reduced visual acuity. The fundus of only one patient exhibited choroid coloboma; in the remaining patients, their fundi exhibited different degrees of irregular retinal depigmentation. The mutation c.360+5G>T in the GPR143 gene was identified in this family. In conclusion, the present study identified the splicing mutation c.360+5G>T in the GPR143 gene in a Chinese family with OA1 and successfully identified the site. To the best of our knowledge, there have been no previous reports regarding this mutation in any major genome databases; therefore, this outcome may enrich the mutation spectrum of the GPR143 gene.
Molecular hydrogen attenuated N-methyl-N-nitrosourea induced corneal endothelial injury by upregulating anti-apoptotic pathway.
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