Circ-NMNAT1 Drives Tumor Progression in Bladder Cancer by Modulating the miR-370-3p/ATXN2L Axis.

The relationship between circular RNAs (circRNAs) and tumor growth and metastasis is increasingly well-established. In this study, we sought to shed light on circ-NMNAT1's potential molecular mechanisms in bladder cancer (BCa). circ-NMNAT1, miR-370-3p, and ATXN2L expression profiles were explored using RT-qPCR and/or Western blot techniques. Cell proliferation was detected by MTT and colony formation assay. Transwell assay was used to detect the migration and invasion ability of cells. Western Blot was used to detect the protein expression level of ATXN2L. The targeting relationship between miR-370-3p and circ-NMNAT1 or ATXN2L was confirmed by dual luciferase reporter gene and RIP assay. A xenograft tumor model was created to investigate circ-NMNAT1's function in BCa in vivo. The high expression of circ-NMNAT1 was measured in BCa. circ-NMNAT1 bound competitively to miR-370-3p and downregulated miR-370-3p expression. After knocking down circ-NMNAT1, the proliferation ability of EJ cells was significantly inhibited, and the number of cell colonies was (80.00 ± 7.10). The number of migrated and invaded cells was significantly reduced by (35.49 ± 0.05)% and (59.00 ± 0.04)%, respectively, after silencing circ-NMNAT1. In addition, downregulation of circ-NMNAT1 also significantly increased the apoptosis rate of EJ cells by (23.55 ± 2.95)%. Knockdown of miR-370-3p or overexpression of ATXN2L reduced the effect of circ-NMNAT1 silencing on BCa cells. The promoting effect of circ-NMNAT1 on BCa progression was further validated in vivo tumor models. The weight and volume of the tumor were significantly inhibited after circ-NMNAT1 knockdown, which were (87.50 ± 20.40) mg and (238.90 ± 21.38) mm, respectively. Circ-NMNAT1 is highly expressed in BCa and promotes the proliferation, migration, and invasion of BCa cells by regulating the miR-370-3p/ATXN2L axis, thereby accelerating the progression of BCa. Our results suggest that circ-NMNAT1 may be a new therapeutic target for BCa.