LINC00473 antagonizes the tumour suppressor miR‐195 to mediate the pathogenesis of Wilms tumour via IKKα. (20th November 2017)

• Record Type: Journal Article
• Authors: Zhu, Shibo; Fu, Wen; Zhang, Liyu; Fu, Kai; Hu, Jinhua; Jia, Wei; Liu, Guochang
• Is Part Of: Cell proliferation. Volume 51:Number 1(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-11-20
• Subjects: IKKα -- LINC00473 -- miR‐195 -- Wilms tumour; Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12416
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: Although 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. Methods: Wilms 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. Results: We 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, IKKα 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/IKKα‐mediated growth inhibition. Conclusion: LINC00473 as an oncogene is up‐regulated to participate into the molecular pathogenesis of Wilms tumour via miR‐195/IKKα.