Evidence suggests that the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in cancer tissues, and its elevated expression is associated with hyperproliferation. However, the underlying mechanisms regarding the role of MALAT1 in retinoblastoma (RB) remain unclear. This study aimed to explore the functional role of MALAT1 in RB by targeting miR-124. The results showed that the expression of MALAT1 was significantly higher in the Y79 cell line than in the ARPE-19 cell line ( < 0.01). Moreover, MALAT1 silence inhibited cell viability, migration, and invasion and promoted apoptosis in Y79 cells ( < 0.05, < 0.01, or < 0.001). miR-124 was upregulated by MALAT1 silence and hence was identified as a target of MALAT1 ( < 0.05 or < 0.001). In addition, miR-124 suppression inhibited cell apoptosis and remarkably abolished the inhibitory effects of MALAT1 silence on cell viability, migration, and invasion ( < 0.05, < 0.01, or < 0.001). In addition, Slug was a target of miR-124 and regulated cell viability, migration, invasion, and apoptosis in Y79 cells ( < 0.05, < 0.01, or < 0.001). Further, Slug silence abolished miR-124 suppression-induced inactivation of the ERK/MAPK and Wnt/β-catenin pathways. Taken together, our data highlight the pivotal role of MALAT1 in RB. Moreover, the present study elucidated the MALAT1-miR-124-ERK/MAPK and Wnt/β-catenin signaling pathways in RB, which might provide a new approach for the treatment of RB.

Insulin resistance, as a common metabolic disorder, may be caused by diet-induced obesity. The aim of the present study is to investigate the effects of dioscin on regulating insulin resistance of adipose tissue induced by a high-fat diet (HFD). An animal model was established successfully using C57BL/6J mice with high-fat feeding, followed by treatment with 5, 10 and 20 mg/kg dioscin through gavage for 18 weeks, and randomly divided into a control group, a HFD model group and a dioscin group treated with 5, 10 and 20 mg/kg/day dioscin for 12 weeks. Histopathological changes in adipose tissues were examined using hematoxylin and eosin staining. Biochemical parameters of the serum were also monitored, including glucose, insulin, total triglyceride, homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (Adipo-IR) levels. Expression of the mRNA and associated proteins of the insulin receptor substrate 1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. HOMA-IR and Adipo-IR values of mice fed with a HFD were significantly higher compared with those in the control group (P<0.01). However, dioscin administration significantly decreased HOMA-IR and Adipo-IR values in a dose-dependent manner (P<0.05), suggesting the effects of dioscin on attenuating insulin resistance. RT-qPCR results indicated that the associated genes of the IRS-1/PI3K/Akt pathway were significantly downregulated by HFD compared with the control group (P<0.05), while dioscin significantly increased the expression of those genes compared with the control group (P<0.05). Similarly, the significant increase in phosphorylated (p-)IRS-1/IRS-1 (P<0.05) and p-Akt/Akt (P<0.05) values were substantially reversed by dioscin treatment. Dioscin pronouncedly mitigated insulin resistance in adipose tissues through the IRS-1/PI3K/Akt pathway and has potential to be used as a novel therapeutic agent for the therapy of HFD-induced insulin resistance in adipose tissue.

High energy-consumption in retinal pigmented epithelium (RPE) cells poses oxidative stress (OS) and contributes to mitochondrial dysfunction (MD) for retinal degeneration-associated diseases. In the present study, we evaluated the protective role of Melatonin, a natural antioxidant, against the hydrogen peroxide (H 2 O 2)-induced damage to RPE cells. The cellular viability, apoptosis, the expression of apoptosis-associated proteins and mitochondrial function were examined in the retinal ARPE-19 cells, post the treatment with H 2 O 2 or (and) with Melatonin. The regulation by Melatonin receptor 1 (MT1) on the Melatonin-mediated protection was also examined via MT1 knockdown with siRNA. Results demonstrated that Melatonin significantly ameliorated cell viability reduction, reduced apoptosis and downregulated the apoptosis-associated proteins in H 2 O 2-treated ARPE-19 cells. The H 2 O 2-induced mitochondrial dysfunction was also significantly blocked by the Melatonin treatment, presenting as a reduced accumulation of reactive oxygen species (ROS) and mitochondrial superoxide and an ameliorated reduction of mitochondrial membrane potential (MMP). In addition, the knockdown of MT1 with MT1-specific siR-NA inhibited the Melatonin-mediated protection against OS damage in ARPE-19 cells. In summary, we confirmed the protective role of Melatonin against H 2 O 2-induced mitochondrial dysfunction in RPE cells. MT1 knockdown blocked such protective role of Melatonin. It is implied that Melatonin exerts a protective role against oxidative stress via Melatonin-MT1 signaling in RPE cells.