Long noncoding RNAs (lncRNAs) are frequently dysregulated and have important roles in many diseases, particularly cancers. lncRNA-HEIH was first identified in hepatocellular carcinoma (HCC). The expression, clinical significance and roles of lncRNA-HEIH in melanoma are still unknown. In the present study, we found that lncRNA-HEIH is highly expressed in melanoma tissues and cell lines, associated with advanced clinical stages, and predicts poor outcomes in melanoma patients. Functional assays showed that ectopic expression of lncRNA-HEIH promotes melanoma cell proliferation, migration and invasion. Knockdown of lncRNA-HEIH inhibits melanoma cell proliferation, migration and invasion. Mechanistically, we revealed that lncRNA-HEIH directly binds to miR-200b/a/429 promoter and represses miR-200b/a/429 transcription. The expression of miR-200b is inversely associated with lncRNA-HEIH in melanoma tissues. Furthermore, overexpression of miR-200b/a/429 abrogates melanoma cell proliferation, migration and invasion enhanced by lncRNA-HEIH. In conclusion, we identified lncRNA-HEIH as a key oncogene in melanoma via transcriptional inhibition of miR-200b/a/429. Our data suggested that lncRNA-HEIH may serve as a promising prognostic biomarker and therapeutic target for melanoma.

BackgroundWe designed and carried out this study to examine the role of miR-155 and the Rheb/mTOR pathway in ischemic stroke. We also investigated how these two elements interact with each other and contribute to injuries resulting from ischemic stroke.Material/MethodsWe used both a middle cerebral artery occlusion rat model in vivo and an oxygen-glucose deprivation cell model in vitro to simulate the onset of ischemic stroke. miR-155 mimics, miR-155 inhibitors, and Rheb siRNA were transfected to alter the expression of miR-155 and Rheb. Infarct sizes were measured using magnetic resonance imaging (MRI) and triphenyltetrazolium chloride (TTC) staining; cell apoptosis rates were calculated using Annexin V-FITC/PI staining and flow cytometry. Levels of miR-155, Rheb, mTOR, and S6K were examined by RT-PCR, immunofluorescence, and western blot. We performed a luciferase activity assay so that the association between miR-155 and Rheb could be fully assessed.ResultsWe demonstrated that miR-155 bound the 3′-UTR of Rheb and suppressed Rheb expression. As suggested by animal models, significant cerebral infarct volumes and cell apoptosis were induced by increased expression of miR-155 and decreased expression of Rheb, mTOR, and p-S6K (P<0.05). miR-155 inhibitors exhibited protective effects on ischemic stroke, including down-regulation of infarction size in cerebral tissues in vivo and reduced apoptosis of BV2 cells in vitro with increased expression of Rheb, mTOR and p-S6K (P<0.05). These protective effects could be substantially antagonized by the transfection of Rheb siRNA (P<0.05).ConclusionsInhibition of miR-155 may play protective roles in ischemic stroke by phosphorylating S6K through the Rheb/mTOR pathway.