摘要: ObjectivesAlthough dramatic improvements of overall survival has achieved in patients with favourable histology Wilms tumour, disease recurrence is still the main cause of cancer-related death in childhood. Long non-coding RNAs (lncRNAs) as oncogenes or tumour suppressors are dysregulated during carcinogenesis. However, the role of lncRNAs in the pathogenesis of Wilms tumour is unknown. Here, an lncRNA LINC00473 signature that functioned as oncogene was identified in Wilms tumour. MethodsWilms tumour (n=15) and relative normal tissues were collected. The LINC00473 expression and function in Wilms tumour was determined. The LncRNA-miRNA network of LINC00473 was analysed in vitro and vivo. ResultsWe uncovered that the expression of LINC00473 was elevated in tumour tissues than that in relative normal tissues. Higher LINC00473 levels correlated to higher stage and unfavourable histology Wilms tumour. Mechanistically, knockdown of LINC00473 inhibited cell vitality and induced Bcl-2-dependent apoptosis and G1/S arrest via CDK2 and cyclin D1. Moreover, LINC00473 harboured binding sites for miR-195 and limited miR-195 availability in a dose-dependent manner. Forced expression of miR-195 impaired tumour survival and metastasis, which, however, could be restored by LINC00473. Furthermore, IKK was the downstream of LINC00473/miR-195 signals and could be directly targeted by miR-195 to participate LINC00473-induced tumour progression. Loss-of-function of LINC00473 in vivo effectively promoted the regression of Wilms tumour via miR-195/IKK-mediated growth inhibition. ConclusionLINC00473 as an oncogene is up-regulated to participate into the molecular pathogenesis of Wilms tumour via miR-195/IKK.

摘要: ObjectivesSteroid-induced osteonecrosis of the femoral head (ONFH) is a common orthopaedic disease of which early detection remains clinically challenging. Accumulating evidences indicated that circulating microRNAs (miRNAs) plays vital roles in the development of several bone diseases. However, the association between circulating miRNAs and steroid-induced ONFH remains elusive. Materials and methodsmiRNA microarray was performed to identify the differentially abundant miRNAs in the serums of systemic lupus erythematosus (SLE) patients with steroid-induced ONFH as compared with SLE control and healthy control group. We predicted the potential functions of these differentially abundant miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and reconstructed the regulatory networks of miRNA-mRNA interactions. ResultsOur data indicated that there were 11 differentially abundant miRNAs (2 upregulated and 9 downregulated) between SLE-ONFH group and healthy control group and 42 differentially abundant miRNAs (14 upregulated and 28 downregulated) between SLE-ONFH group and SLE control group. We also predicted the potential functions of these differentially abundant miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and reconstructed the regulatory networks of miRNA-mRNA interactions. ConclusionsThese findings corroborated the idea that circulating miRNAs play significant roles in the development of ONFH and may serve as diagnostic markers and therapeutic targets.