| Popis: |
Objectives A subclass of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involve in cancer progression. This work aimed to investigate the influence and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). Materials and methods The miR-497 and miR-195 were derived from MIR497HG. Cell proliferation, migration and invasion assays were used to measure the function of MIR497HG, miR-497 and miR-195 in BCa. Bioinformatics, RT-qPCR, western blot, luciferase reporter assay, ChIP, and so on, were used to reveal the upstream and downstream mechanisms of MIR497HG in BCa. Results We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing TCGA and our dataset. MIR497HG overexpression inhibited BCa cell proliferation, migration and invasion in vitro. MiR-497/miR-195 inhibitor rescued significantly the inhibiton effects of overexpression of MIR497HG in BCa. Mechanistically, miR-497 and miR-195 coordinately suppressed multiple key components in Hippo/Yap and TGF-β signaling, and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proved to be critical for silencing MIR497HG transcription in BCa cells. Conclusions We propose for the first time that MIR497HG suppressed BCa progression and its upstream and downstream mechanisms. Blocking the pathological process may be a potential strategy for the treatment of BCa. |
