LINC01451 drives epithelial-mesenchymal transition and progression in bladder cancer cells via LIN28/TGF-β/Smad pathway

Background: The pathogenesis of bladder cancer (BLCa) is still unclear. Long non-coding RNAs (lncRNAs) participate in diverse biological processes across every branch of life, especially in cancer. Dysregulated lncRNAs in BLCa and their biological significance require further investigations. Methods: Herein, a differential expression profile of lncRNAs in BLCa was conducted by microarray data. The expression level of lncRNA LINC01451 in 70 pairs of BLCa tissue samples and different BLCa cell lines were analyzed via real-time quantitative PCR. The CRISPR-CAS9 technique was employed to establish the LINC01451 stably transfected cell lines. Loss-of-function, as well as gain-of-function assays were carried out to evaluate the effects of LINC01451 on cell proliferation, migration, and invasion. Patient-derived xenograft (PDX) mouse models were adopted in the in vivo experiments. Western blot, biotinylated RNA probe pull-down assay, fluorescence in situ hybridization, and immunohistochemistry were utilized to assess the underlying molecular mechanisms of LINC01451 in BLCa. Results: LINC01451 was identified a novel functional lncRNA, whose expression level in BLCa tissues was significantly higher compared with the normal tissues. Furthermore, it was found that LINC01451 directly docked LIN28A and LIN28B, and promoted the proliferation, invasion, and metastasis of BLCa. Mechanistically, LINC0145 was shown to depend on LIN28A and LIN28B, facilitated epithelial-mesenchymal transition (EMT) through activating the TGF-beta/Smad signaling pathway, which subsequently aggravated BLCa progression. Conclusions: We demonstrates that LINC01451 drives EMT-induced BLCa progression by activating the LIN28/ TGF-beta/Smad signaling pathway. Promisingly, LINC01451 acts as a prognostic biomarker and a novel therapeutic target for BLCa.

Automated summary

This study identified LINC01451 as a functional lncRNA with significantly higher expression in BLCa tissues compared to normal tissues. LINC01451 was found to directly interact with LIN28A and LIN28B, promoting proliferation, invasion, and metastasis of BLCa. Mechanistically, LINC01451 was shown to facilitate epithelial-mesenchymal transition through activating the TGF-beta/Smad signaling pathway, leading to the progression of BLCa.