Background: This study aimed to investigate the function of circular RNA SMARCA5 (circ-SMARCA5) on cell proliferation, apoptosis, migration and invasion in bladder cancer. Methods: Ten pairs of human bladder cancer tissue and adjacent tissue, five human bladder cancer cell lines (including TCCSUP, 5637, J82, UM-UC-3 and T-24) and normal human urothelial cell line SV-HUC-1, were obtained for the detection of circ-SMARCA5. Control overexpression and ShRNA, circ-SMARCA5 overexpression and ShRNA were constructed and transfected into UM-UC-3 cells as Control(+), Control(−), Circ-SMARCA5(+) and Circ-SMARCA5(−) groups. The role of circ-SMARCA5 was investigated in terms of cellular proliferation, apoptosis, migration, and invasion. Results: Circ-SMARCA5 was overexpressed in tumor tissue compared to paired adjacent tissue and it was also overexpressed in TCCSUP, 5637, J82 and UM-UC-3 cells compared to normal human urothelial cell line SV-HUC-1. In UM-UC-3 cells, cell proliferation ability, migration rate and invasion cell count were increased in Circ-SMARCA5(+) group compared to Control(+) group, while reduced in Circ-SMARCA5(−) group compared to Control(−) group. Regarding the cell apoptosis, apoptosis rate and apoptotic protein C-Caspase 3 expression were decreased in Circ-SMARCA5(+) group than those in Control(+) group but raised in Circ-SMARCA5(−) group compared to Control(−) group, meanwhile, the anti-apoptotic protein Bcl-2 expression was elevated in Circ-SMARCA5(+) group than that in Control(+) group but reduced in Circ-SMARCA5(−) group compared to Control(−) group. Conclusions: Circ-SMARCA5 is overexpressed, and promotes cell proliferation, migration and invasion, but represses apoptosis in bladder cancer.

Background Chemoresistance is a main limitation in chemotherapy for therapeutic cancer. MicroRNA (miRNA) has been indicated in the progression and tumorigenesis of many types of cancer, but the effect of miR-34b-3p in bladder cancer (BCa) cells is still unknown. Material/Methods This research compared the multidrug-sensitive (5637) BCa cell line and the multidrug-resistant (EJ) BCa cell line. We found that CCND2 (G1/S-specific cyclin-D2) and P2RY1 (purinergic receptor P2Y1) were the targets of miR-34b-3p, as further validated by qRT-PCR (quantitative real-time polymerase chain reaction) and western blot analysis. Results Forced reversal of the levels of miR-34b-3p or CCND2/P2RY1 changed the chemoresistance profiles in both 5637 cells and EJ cells. Further experiments suggested that the CCND2 gene and the P2RY1 gene act in concert to negatively correlate with miR-34b-3p effect on BCa multidrug-chemoresistance. Conclusions These results not only reveal new players regulating BCa chemoresistance, but also provide clues for effective chemotherapy for BCa patients.

Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.